[{"id":63,"uid":"NPDI-yBr48Q","name":"The Effects of Berberine on the Pharmacokinetics of Ciclosporin A in Healthy Volunteers","napdiIdentifier":"PMID: 16541194","overallSummary":"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 &lt; 0.05) and the mean C12 increased to 123 microg/l from 104 microg/l (P &lt; 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.","pubmedId":16541194,"embaseId":null,"croIdentifier":"Wuhan General Hospital","croInformation":"Department of Clinical Pharmacology","dateStart":null,"dateEnd":null,"internalComment":null,"status":"published","compoundId":null,"naturalProductUid":"NP-002d7e9a-2baf-47cb-a936-51ba9cbb36a7","naturalProductSampleId":null,"studySourceTypeId":1,"naturalProduct":{"uid":"NP-002d7e9a-2baf-47cb-a936-51ba9cbb36a7","binomial":"Hydrastis canadensis","name":"Goldenseal","itis":null,"srs":"66690655-f406-4d67-96e3-2066aafee8d5","source_id":"","conceptId":null},"compound":null,"studySourceType":{"id":1,"name":"Published report"},"experiments":[{"id":285,"uid":"NPDI-FJjrAg","name":"CsA 6 mg/kg Experiment","overallEffect":0,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":null,"experimentalConditionsComment":"1 mL ulnar vein draws<br />Subjects not taking any medications","resultsComment":"Converted Cmax, C12 and AUC from microgram/L to ng/mL (same decimal placement). C (plasma) taken at 12 hours.","internalComment":null,"objectCompoundId":122,"objectMetaboliteCompoundId":null,"precipitantCompoundId":80,"cytochromeB5Id":null,"studyId":63,"experimentTypeId":9,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType":{"id":9,"name":"In Vivo Interaction","isInVitro":false,"isTransporter":false,"isEnzyme":false,"purl":"http://purl.obolibrary.org/obo/DIDEO_00000071"},"objectCompound":{"id":122,"name":"cyclosporin a","unii":null,"inChIKey":"PMATZTZNYRCHOR-CGLBZJNRSA-N","publicDescription":null,"internalComment":null,"conceptId":null,"enantiomerOfId":null},"precipitantCompound":{"id":80,"name":"berberine","unii":null,"inChIKey":"YBHILYKTIRIUTE-UHFFFAOYSA-N","publicDescription":null,"internalComment":null,"conceptId":19012197,"enantiomerOfId":null},"objectMetaboliteCompound":null,"enzymes":[{"id":13,"name":"CYP3A4","conceptId":4306811,"experiment_enzyme_xref":{"enzymeId":13,"experimentId":285}}],"transporters":[{"id":11,"name":"P-gp (ABCB1)","conceptId":null,"experiment_transporter_xref":{"experiment":285,"transporte":11}}],"quantifiedMetabolites":[]},{"id":286,"uid":"NPDI-6IV4Kg","name":"CsA 3 mg/kg Experiement","overallEffect":1,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":null,"experimentalConditionsComment":null,"resultsComment":"Converted Cmax, Cplasma (C12) and AUC from microgram/L to ng/mL (same decimal placement)","internalComment":null,"objectCompoundId":122,"objectMetaboliteCompoundId":null,"precipitantCompoundId":80,"cytochromeB5Id":null,"studyId":63,"experimentTypeId":9,"testSystemId":null,"ic50ShiftExperimentId":null,"controlDataExperimentId":null,"controlDataForExperimentId":null,"naturalProductSampleId":null,"experimentType":{"id":9,"name":"In Vivo Interaction","isInVitro":false,"isTransporter":false,"isEnzyme":false,"purl":"http://purl.obolibrary.org/obo/DIDEO_00000071"},"objectCompound":{"id":122,"name":"cyclosporin a","unii":null,"inChIKey":"PMATZTZNYRCHOR-CGLBZJNRSA-N","publicDescription":null,"internalComment":null,"conceptId":null,"enantiomerOfId":null},"precipitantCompound":{"id":80,"name":"berberine","unii":null,"inChIKey":"YBHILYKTIRIUTE-UHFFFAOYSA-N","publicDescription":null,"internalComment":null,"conceptId":19012197,"enantiomerOfId":null},"objectMetaboliteCompound":null,"enzymes":[{"id":13,"name":"CYP3A4","conceptId":4306811,"experiment_enzyme_xref":{"enzymeId":13,"experimentId":286}}],"transporters":[{"id":11,"name":"P-gp (ABCB1)","conceptId":null,"experiment_transporter_xref":{"experiment":286,"transporte":11}}],"quantifiedMetabolites":[]}]}]