大鼠肝微粒体中美西律对映体氧化代谢的立体选择性研究

Study on the stereoselectivity of oxidation metabolism of mexiletine enantiomers in rat liver microsome

目的测定大鼠肝微粒体中R-(-)-和S-(+)-美西律体外氧化代谢的立体选择性。方法将(±)-美西律与大鼠肝微粒体孵育后,采用柱前衍生化毛细管气相色谱-氢火焰离子化检测法测定了酶促反应的时间曲线及动力学参数Vm和Km值。结果在大鼠肝微粒体中,美西律的两个对映体的Vm和Km值均有显著性差异(P<0.01)。结论美西律在大鼠肝微粒体中的氧化代谢具有对映体选择性。

OBJECTIVE To Study the stereoselectivity of oxidation metabolism of mexiletine enantiomers in rat liver mlcrosome. METHODS The time course and the parameters of enzymatic kinetics of mexiletine enantiomers, Vm and Km, were determined by a capillary gas chromatographic system with flame ionization detection. RESULTS There were significant differences between R-（ - ） - mexiletine and S-（ ＋ ）-mexiletine enantiomer for their Vm and Km. CONCLUTION The oxidation metabolism of mexiletine enantiomers shows stereoselectivity in rat liver microsome.