Effects of berberine on the blood concentration of cyclosporin A in renal transplanted recipients: clinical and pharmacokinetic study
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To study the effects of berberine (BBR) on the blood concentration and pharmacokinetics of cyclosporin A (CsA) in renal-transplant recipients.
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.
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<0.05). As for the BBR-free group, they rose by 64.5% and 69.4%, respectively, relative to those at baseline (P<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<0.05). No significant effects on liver or renal functions were observed under coadministration of BBR. After co-administration of BBR in six patients for 12 days, the mean AUC of CsA was increased by 34.5% (P<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<0.05). The average percentage increases in the steady-state drug concentration (Css) and minimum blood concentration (Cmin) were 34.5% and 88.3%, respectively (P<0.05). In addition, the average percentage decrease in CL/F was 40.4% (P<0.05) and the peak-to-through fluctuation index was significantly reduced (P<0.01).
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.
KeywordsRenal transplantation Cyclosporin A Berberine Drug interaction Pharmacokinetics
- 10.Proppe DG, Hoch OD, McLean AJ, Visser KE (1995) Influence of chronic ingestion of grapefruit juice on steady state blood concentration of cyclosporine A in renal transplant patients with stable graft function. Br J Clin Pharmacol 39:337–338Google Scholar
- 15.Wu XC, Xin HW, Li Q, Yu AR, Zhong MY, Tang K (2003) Pharmacokinetics of cyclosporine A coadministrated with berberine in Chinese healthy volunteers. Chin J Hosp Pharm 23:707–709Google Scholar
- 16.Li Q, Wu XC, Xin HW, Yu AR, Zhong MY, Leng JH, Jiang ZJ, Zhu M, Tang LG, Xie S (2001) Clinical study on coadministration of cyclosporin A and berberine hydrochloride in renal transplanted recipients. Chin J Clin Pharmacol 17:114–117Google Scholar
- 18.Wilms HW, Straeten V, Lison AE (1988) Different pharmacokinetics of cyclosporine A early and late after renal transplantation. Transpl Proc 20(2 Suppl 2):481–484Google Scholar
- 19.Xin HW, Wu XC, Li Q, Zhong MY, Yu AR, Zhu M (2002) Effects of berberine hydrochloride and coadministration with cyclosporine A on liver microsomal cytochrome P450 isoenzyme in mice. Chin Pharm J 37:496–499Google Scholar
- 20.Xin HW, Wu XC, Li Q, Yu AR, Zhong MY, Zhu M, Liu YY (2002) Effects of coadministration of berberine chloride with cyclosporin on liver microsomal cytochrome P450 isoenzyme and mdr1 in rats. Chin Pharmacol Bull 18:397–401Google Scholar