五味子甲素对大鼠肝微粒体CYP3A活性的影响

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

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。

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 micvosome was as a carrier. The IC50 value of schizandrin A by in vitro administration and Mated 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 IC50 of schizandfin A on MDZ metabolism in liver mierosomes was 6.26 1μmol/mL, and the enzyme kinetic parameters were as follows： Km = 15.77 μmol/L, Ki = 5.5 μmol/mL. CONCLUSION： Sehizandrin A is able to inhibit CYP3A activity in rat liver miemsomes. The inhibition is mixed type, non-competitive and anticompetitive inhibition.