Goldenseal (Hydrastis canadensis) 43525850
The Effects of Berberine on the Pharmacokinetics of Ciclosporin A in Healthy Volunteers CSV JSON

The effects of berberine (BBR) on the pharmacokinetics of ciclosporin A (CsA) were examined in healthy volunteers. Six healthy male volunteers were orally treated with 0.3 g BBR, twice daily for 10 days. Pharmacokinetic investigations on CsA at 6 mg/kg were done both before and at the end of the BBR treatment period. Another six healthy male volunteers were involved in the pharmacokinetic study with 3 mg CsA/kg, in which the subjects orally received the second single dose of 3 mg CsA/kg, followed by a single oral dose of 0.3 g BBR. The blood CsA concentrations were determined by fluorescence polarization immunoassay. In the pharmacokinetic study with 6 mg CsA/kg, BBR caused no significant changes in the pharmacokinetic parameters of CsA. However, in the trial with 3 mg CsA/kg, the average percentage increase in area under the blood concentration-time curve of CsA was 19.2% (P < 0.05) and the mean C12 increased to 123 microg/l from 104 microg/l (P < 0.05), without altering elimination half-life (t(1/2)), maximum blood drug concentration (Cmax), time to Cmax (tmax), apparent oral clearance (CL/F). The present results suggest that BBR can increase the oral bioavailability of CsA at the dosage of 3 mg/kg. The BBR-mediated increase in CsA bioavailability may be partly attributed to a decrease in liver and/or intestinal metabolism through the inhibition of CYP3A4 in the liver and/or gut wall. The BBR-induced increase in emptying time of stomach and small intestine might be another reason for the increase in CsA bioavailability. However, the speculation should be proved by further investigation.

1 . CsA 3 mg/kg Experiement (id=NPDI-6IV4Kg)

In Vivo Interaction Study

Increased systemic exposure was detected.

cyclosporin A

Berberine 19012197

  • CYP3A4 4306811
  • P-gp (ABCB1)

Results

Converted Cmax, Cplasma (C12) and AUC from microgram/L to ng/mL (same decimal placement)

Compound measured Measurement Value Study sequence Additional information N replicates

Experimental Conditions

Parallel
Single dosing

Population

Healthy volunteers
Males

Nonsmokers

6

Age (SD): 22.8 (2.2) years
Ht (SD): 173 (4.6) cm
Wt (SD): 64.3 (8.1) kg

Pharmacokinetic (PK) Sampling Information

0.5, 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours

Drug or Natural Product Administration

Object Administration — cyclosporin A

Oral

not specified

3 mg/kg

Twice in total - one dose at day 0 and one dose at day 15

15 days

Precipitant Administration — Berberine

Oral

not specified

600 mg

BID

10 days (after 3 day washout of CsA first dose)

Natural Product Characteristics

Shanghai Tianpin Pharmaceutic Factory, Chine

not specified

Pharmacodynamics (PD) & Adverse Events

Gastrointestinal disorders 35800000

Stomach upset and diarrhea

Gastrointestinal disorders 35700000

2 . CsA 6 mg/kg Experiment (id=NPDI-FJjrAg)

In Vivo Interaction Study

No Effect (based on bioequivalence limits) was detected.

cyclosporin A

Berberine 19012197

  • CYP3A4 4306811
  • P-gp (ABCB1)

Results

Converted Cmax, C12 and AUC from microgram/L to ng/mL (same decimal placement). C (plasma) taken at 12 hours.

Compound measured Measurement Value Study sequence Additional information N replicates

Experimental Conditions

1 mL ulnar vein draws
Subjects not taking any medications

Parallel
Single dosing

Population

Healthy volunteers
Males

Nonsmokers

6

Age (SD): 22.8 (2.2) years
Ht (SD): 173 (4.6) cm
Wt (SD): 64.3 (8.1) kg

Pharmacokinetic (PK) Sampling Information

0.5, 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours

Drug or Natural Product Administration

Object Administration — cyclosporin A

Oral

not specified

6 mg/kg

Twice in total - one dose at day 0 and one dose at day 15

15 days

Precipitant Administration — Berberine

Oral

not specified

600 mg

300 mg BID

10 days (after 3-day washout of CsA first dose)

Natural Product Characteristics

Shanghai Tianpin Pharmaceutic Factory, Chine

Not specified

Pharmacodynamics (PD) & Adverse Events

Gastrointestinal disorders 35800000

Stomach upset and diarrhea

Gastrointestinal disorders 35700000