五味子甲素对大鼠肝微粒体CYP3A活性的影响

目的：通过体外药物代谢实验探讨五味子甲素对CYP3A活性的影响。方法：以大鼠肝微粒体为载体，选取咪达唑仑（MDZ）作为药物“探针”，建立高效液相色谱（HPLC）检测方法，体外给药测定五味子甲素对MDZ的IC50值以及相关酶动力学参数。结果：孵育体系内源性物质不干扰测定，方法快捷、稳定、灵敏度高。在肝微粒中，五味子甲素对MDZ的IC50浓度为6．26μmol／mL，相关酶动力学参数：Km=15．77μmol／L，Ki=5．50μmol／mL。结论：五味子甲素对大鼠肝微粒体CYP3A活性具有抑制作用，其抑制作用为混合型，即：非竞争与反竞争抑制。

Effects of schizandrin A on the activity of CYP3A in rat liver microsomes

AIM:To study the effects of schizandrin A on CYP3A by in vitro drug metabolism experiments.METHODS:Midazolam(MDZ)was adopted as a drug "probe" and a detection method of high-performance liquid chromatography(HPLC)was established,the rat liver microsome was as a carrier.The IC_(50) value of schizandrin A by in vitro administration and related enzyme kinetic parameters on CYP3A were detected.RESULTS:The endogenous substances did not interfere with the determination in the incubation system.The method was fast,stable and had high sensitivity.The IC_(50) of schizandrin A on MDZ metabolism in liver microsomes was 6.26 μmol/mL,and the enzyme kinetic parameters were as follows:K_m=15.77 μmol/L,K_i =5.5 μmol/mL.CONCLUSION:Schizandrin A is able to inhibit CYP3A activity in rat liver microsomes.The inhibition is mixed type,non-competitive and anticompetitive inhibition.