[通过鸡尾酒探针药物在人肝微粒体混合物中研究小檗碱对细胞色素P450酶的抑制作用]
[CYP450 enzyme inhibition of berberine in pooled human liver microsomes by cocktail probe drugs].
作者信息
Chen Jian-Long, Zhang Yu-Ling, Dong Yu, Gong Ji-Yu, Cui Han-Ming
机构信息
Changchun University of Traditional Chinese Medicine, Changchun 130117, China.
出版信息
Zhongguo Zhong Yao Za Zhi. 2013 Jun;38(12):2009-14.
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 microg x L(-1). The pharmacokinetics of dextromethorphan was significantly decreased when the concentration of berberine was exceed 200 microg x L(-1).
CONCLUSION
Berberine has no influence on the activities of CYP3A4, CYP1A2 and CYP2C19 below 2 000 microg x L(-1), but can inhibit the activity of CYP2E1 and CYP2D6 in concentration-dependent.
目的
采用鸡尾酒探针药物研究小檗碱对人肝微粒体中CYP450酶的抑制作用。
方法
建立鸡尾酒探针药物法，建立LC-MS/MS分析方法，以测定咪达唑仑、非那西丁、右美沙芬、甲苯磺丁脲、氯唑沙宗5种探针及内标苯海拉明，评价小檗碱给药后人肝微粒体中CYP450活性的变化。
结果
与对照组相比，咪达唑仑、非那西丁和甲苯磺丁脲的药代动力学无显著差异，但氯唑沙宗的药代动力学显著降低。当小檗碱浓度为50μg·L⁻¹时，右美沙芬的药代动力学无显著差异。当小檗碱浓度超过200μg·L⁻¹时，右美沙芬的药代动力学显著降低。
结论
小檗碱在浓度低于2000μg·L⁻¹时对CYP3A4、CYP1A2和CYP2C19的活性无影响，但可浓度依赖性抑制CYP2E1和CYP2D6的活性。
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