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Effects of berberine on the blood concentration of cyclosporin A in renal transplanted recipients: clinical and pharmacokinetic study

  • Pharmacokinetics and Disposition
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

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 (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).

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.

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Authors and Affiliations

  1. Department of Clinical Pharmacology, Wuhan General Hospital, Wuhan, 430070, China

    Xiaochun Wu, Qing Li, Huawen Xin, Airong Yu & Mingyuan Zhong

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  1. Xiaochun Wu
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  2. Qing Li
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  3. Huawen Xin
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  4. Airong Yu
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  5. Mingyuan Zhong
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Correspondence to Xiaochun Wu.

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Wu, X., Li, Q., Xin, H. et al. Effects of berberine on the blood concentration of cyclosporin A in renal transplanted recipients: clinical and pharmacokinetic study. Eur J Clin Pharmacol 61, 567–572 (2005). https://doi.org/10.1007/s00228-005-0952-3

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  • DOI: https://doi.org/10.1007/s00228-005-0952-3

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