Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.
Authors proposed mechanism:
Inhibitory effect of berberine on CYP2D6 activity may be caused by substrate competition.
CYP2C9 did not metabolize berberine, further study about berberine and CYP2C9 gene regulation may provide evidence to clarify this alteration.
CYP3A4 inhibition might be caused by berberine slowing the motility of the digestive system or suppressed mRNA expression
Abstract:
Purpose Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interac- tions between berberine-containing products and cyto- chromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.
Methods A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.
Results A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P< 0.05); and the phenotypic indices of 1 h midazolam/1′- hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.
Conclusions Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.