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目的 阐明盐酸小檗碱与环孢素A合用对药物代谢酶的影响.方法 采用分光光度法测定盐酸小檗碱、环孢素A及二者合用时小鼠肝微粒体CYP450、ERD、ADM和GST的含量或活性.结果 ig给药3和6 d,盐酸小檗碱(200mg/kg)对CYP450、ERD没有明显的抑制作用,但对ADM和GST有抑制作用;环孢素A(45 mg/kg)对ERD、ADM和GST均有抑制作用;盐酸小檗碱与环孢素A合用对CYP450、ERD、ADM和GST均有明显抑制作用.结论 盐酸小檗碱与环孢素A的组合是药物代谢酶CYP450、ERD(CYP3A)、ADM(CYP1A1、2B1、2C11)和GST的强抑制剂,其总体抑制水平至少与已知的抑制剂酮康唑和硝苯地平相当甚至更强.
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[Abstract]
Object To expound the effects of coadministration of berberine hydrochloride (BBH) and cyclosporine A (CsA) on liver microsomal drug metabolizing enzymes in mice. Methods The contents and activities of coadministration of BBH and CsA on hepatic microsomal cytochrome P450 (CYP450), erythromycin demethylase (ERD), aminopyrence N demethylase (ADM) and glutathiones S transferase (GST) were determined by spectrophotometry. Results BBH at 200 mg/kg had no significant inhibitory effects on CYP450 and ERD, but it exhibited the inhibitory actions on ADM and GST after ig for 3 or 6 d in mice. CsA at 45 mg/kg could markedly inhibit ERD, ADM and GST. And the significant inhibitory effects on CYP450, ERD, ADM and GST were observed in the coadministration of BBH and CsA, respectively. Conclusion The combination of BBH and CsA is a powerful inhibitor on drug metabolizing enzymes such as CYP450, ERD (CYP3A), ADM (CYP1A1, 2B1, 2C11) and GST. Its inhibitory effect is at least equal to (even stronger than) that of Ketoconazole and Nifedipine which are known as the inhibitors of drug metabolizing enzymes.
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