[{"id":72,"uid":"NPDI-rmRb0A","name":"Effects of berberine on the blood concentration of cyclosporin A in renal transplanted recipients: clinical and pharmacokinetic study","napdiIdentifier":"PMID: 16133554","overallSummary":"<div class=\"page\" title=\"Page 1\">\r\n<div class=\"layoutArea\">\r\n<div class=\"column\">\r\n<p>Objective: To study the effects of berberine (BBR) on the blood concentration and pharmacokinetics of cyclosporin A (CsA) in renal-transplant recipients.<br />Methods: In a randomized and controlled clinical trial, 52 renal-transplant recipients were treated with CsA and 0.2 g BBR three times daily for 3 months, while another 52 subjects received CsA without BBR co-administration. Blood trough concentration of CsA and biochemistry indexes for hepatic and renal functions were determined. For the pharmacokinetic study, six renal transplant recipients were included with a 3-mg/kg dosage of CsA twice daily before and after oral co- administration of 0.2 g BBR three times daily for 12 days.<br />Results: The trough blood concentrations and the ratios of concentration/dose of CsA in the BBR-treated group increased by 88.9% and 98.4%, respectively, compared with those at baseline (P&lt;0.05). As for the BBR-free group, they rose by 64.5% and 69.4%, respectively, relative to those at baseline (P&lt;0.01). Nevertheless, the final blood concentrations and the ratios of concentration/dose of CsA in BBR-treated patients were still 29.3% and 27.8%, respectively, higher than those in BBR-free patients (P&lt;0.05). No significant effects on liver or renal functions were observed under coadministration of BBR. After co-administra- tion of BBR in six patients for 12 days, the mean AUC of CsA was increased by 34.5% (P&lt;0.05). The mean time taken to reach the peak blood concentration (tmax) and the mean half-life (t1/2) of CsA were increased by 1.7 h and 2.7 h, respectively (P&lt;0.05). The average percentage increases in the steady-state drug con- centration (Css) and minimum blood concentration (Cmin) were 34.5% and 88.3%, respectively (P&lt;0.05). In addition, the average percentage decrease in CL/F was 40.4% (P&lt;0.05) and the peak-to-through fluctuation index was significantly reduced (P&lt;0.01). <br /><br />Conclusion: The BBR can markedly elevate the blood concentration of CsA in renal-transplant recipients in both clinical and pharmacokinetic studies. This combination may allow a reduction of the CsA dosage. The mechanism for this interaction is most likely explained by inhibition of CYP3A4 by BBR in the liver and/or small intestine.</p>\r\n</div>\r\n</div>\r\n</div>","pubmedId":16133554,"embaseId":null,"croIdentifier":"Wuhan General Hospita","croInformation":"Wuhan General Hospita","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":295,"uid":"NPDI-uJn2xw","name":"CsA in Renal Transplant patients","overallEffect":1,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":null,"experimentalConditionsComment":null,"resultsComment":"Table 5<br /><br />Fluctuation Index: Control - 2.8 (0.6) Test 1.4 (0.7) p&lt;0.01","internalComment":null,"objectCompoundId":122,"objectMetaboliteCompoundId":null,"precipitantCompoundId":80,"cytochromeB5Id":null,"studyId":72,"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":[],"transporters":[],"quantifiedMetabolites":[]},{"id":296,"uid":"NPDI-C2C-Nw","name":"CsA Trough measurements in 52 patients","overallEffect":1,"isControlData":false,"isIc50Shift":false,"croCutoff":null,"croIdentifier":null,"comment":null,"experimentalConditionsComment":null,"resultsComment":null,"internalComment":null,"objectCompoundId":122,"objectMetaboliteCompoundId":null,"precipitantCompoundId":80,"cytochromeB5Id":null,"studyId":72,"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":[],"transporters":[],"quantifiedMetabolites":[]}]}]