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作 者 ：陈健龙,张玉玲,董宇,贡济宇,崔翰明

期 刊 ：中国中药杂志 2013年 38卷 12期 页码：2009.

关键词：鸡尾酒法；探针药物；混合人肝微粒体；小檗碱；P450酶抑制；

Keywords:cocktail, probe drugs, pooled human liver microsomes, berberine, CYP450 enzyme inhibition,

摘 要 ：目的: 研究小檗碱对人肝微粒体CYP活性的影响. 方法: 以苯海拉明为内标,建立LC-MS/MS同时测定5种探针药物:咪达唑仑、非那西丁、右美沙芬、甲苯磺丁脲和氯唑沙宗的含量,采用鸡尾酒(cocktail)法探针药物法评价不同浓度小檗碱对混合人肝微粒体CYP不同亚型活性的影响. 结果: 与对照组相比,咪达唑仑、非那西丁和甲苯磺丁脲的代谢速率基本没有变化,而氯唑沙宗的代谢速率明显变慢,对于右美沙芬,当小檗碱的质量浓度为50 μg·L^-1时,其代谢速率基本没有变化,当小檗碱的质量浓度大于200 μg·L^-1时,其代谢速率明显变慢. 结论: 小檗碱质量浓度在2 000 μg·L^-1以下时对人肝微粒体中CYP3A4,CYP1A2和CYP2C9活性没有明显影响,但对CYP2E1和CYP2D6有明显的浓度依赖性抑制作用.

Abstract:Objective: To investigate the effect of CYP450 enzyme inhibition of berberine in pooled human liver microsomes by cocktail probe drugs. Method: Cocktail probe drugs method has been established, an LC-MS/MS analytical method has been established to determine the five probes of midazolam, phenacetin, dextromethorphan, tolbutamide, chlorzoxazone and the internal standard was benzhydramine to evaluate the effect of CYP450 activity following administration of berberine in pooled human liver microsomes. Result: Compared with control group,the pharmacokinetics of midazolam, phenacetin and tolbutamide were no significant differences, but the pharmacokinetics of chlorzoxazone was significantly decreased. There were no significant differences for the pharmacokinetics of dextromethorphan when the concentration of berberine was 50 μg·L^-1.The pharmacokinetics of dextromethorphan was significantly decreased when the concentration of berberine was exceed 200 μg·L^-1. Conclusion: Berberine has no influence on the activities of CYP3A4, CYP1A2 and CYP2C19 below 2 000 μg·L^-1, but can inhibit the activity of CYP2E1 and CYP2D6 in concentration-dependent.

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