左归饮对大鼠体内Cyp3a1、Cyp2d2、Cyp1a2代谢酶活性的研究

A Study on the Effect of Zuoguiyin on Metabolic Enzymes Activity of Cyp3a1,Cyp2d2 and Cyp1a2 in Rats

目的:全面系统地探讨左归饮对大鼠体内3种细胞色素P450酶不同亚型体内代谢活性的影响,为临床安全、合理用药提供基础研究。方法:采用Cocktail探针药物法,结合LC-MS/MS检测技术,选择咪达唑仑、氢溴酸右美沙芬、非那西丁作为探针底物,研究左归饮对大鼠肝脏细胞色素P450不同亚型Cyp3a1、Cyp2d2、Cyp1a2活性的影响。结果:建立的LC-MS/MS方法,可以同时测定3种探针药物非那西丁、氢溴酸右美沙芬及咪达唑仑在大鼠体内的血药浓度。各吸收峰分离完全,线性关系良好,准确度、精密度及稳定性均符合生物样本检测要求,操作简便。同空白组相比,实验组咪达唑仑和氢溴酸右美沙芬的主要药动学参数T1/2、V、CL、AUC(0~t)和AUC(0~∞)有显著性差异,而非那西丁无显著性差异。结论:左归饮在大鼠体内对Cyp3a1酶和Cyp2d2酶活性有诱导作用,对Cyp1a2无显著影响。

Objective： To comprehensively and systematically study the effect of Zuoguiyin on the vivo meta- bolic activity of three different subtypes of cytochrome p450 enzymes in rats in order to provide basic research for clinical safety and rational use of drugs. Methods： Cocktail probe drug method was taken. Combined with LC- MS / MS detection technique and taken midazolam, dextromethorphan hydrobromide, phenacetin as probe sub- strate, the effect of Zuoguiyin on the activity of cytoolasm P450 in different subtvoes of Cvo3al. Cvo2d2 and Cypla2 in rat liver was studied. Results： The established LC-MS/MS method was used to determine the plasma concentrations of phenacetin, dextromethorphan hydrobromide and midazolam in the rats. The absorption peaks were completely separated, the linear relationship was good. The accuracy, precision and stability were in ac- cordance with the requirements of biological samples, and the operation is simple. Compared with the blank group, there were significant difference in the main pharmacokinetic parameters T1/2, V, EL, AUC（0-t） and AUC（0-∞） of darazapram and hydrobromide in the experiment group, while there was no significant difference in Sididine. Conclusion： Zuoguiyin has an inductive effect on the activity of Cyp3al and 2d2 in vivo, while it has no significant effect on Cypla2.