氧氟沙星I相代谢的立体选择性

Determination of the Stereoselectivity for Phase I Metabolism of S (-) and R (+) Ofloxacin by RP HPLC

目的：测定Ｓ－（－ ）－和Ｒ－（＋ ）－氧氟沙星（ＯＦＬＸ）体外Ｉ相代谢的立体选择性。方法：分别将Ｓ－（－ ）－和Ｒ－（＋ ）－ＯＦＬＸ与大鼠肝微粒体孵育后，采用反相高效液相色谱方法，测定代谢物随反应时间的生成曲线和酶动力学参数（最大反应速度、米氏常数，清除率）。结果：Ｓ－（－ ）－ＯＦＬＸ代谢物的生成量和生成速度均大于Ｒ－（＋ ）－ＯＦＬＸ，两对映体的酶动力学参数也有显著差异。结论：Ｓ－（－ ）－ＯＦＬＸ和Ｒ－（＋ ）－ＯＦＬＸ在大鼠肝微粒体中的Ｉ相代谢具有立体选择性。

Objective:To determine the stereoselectivity for phase I metabolism of S (-) and R (+) ofloxacin(OFLX) in vitro.Methods:The curves of reaction time vs.metabolites formed and the parameters of enzymatic kinetics for both enantiomers were determined by using reserve phase high performance liquid chromatography after S (-) or R (+) OFLX was incubated with rat liver microsome respectively.Results:The formation rate of metabolites for S (-) OFLX was faster than that for R (+) OFLX.There were significant differences between two enantiomers for their Vmax,Km and Clint.Conclusion:The phase I metabolism of S (-) and R (+) OFLX in rat liver microsome possessed stereoselectivity.