Objective: To study the effects of berberine (BBR) on the blood concentration and pharmacokinetics of cyclosporin A (CsA) in renal-transplant recipients.
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.
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 < 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 (t(max)) and the mean half-life (t(1/2)) 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).
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.