苯巴比妥诱导对普罗帕酮体外Ⅰ相代谢的立体选择性影响

Stereoselective Induction of PhaseⅠMetabolism of Propafenone in Rat Liver Microsome by Phenobarbital

目的 :观察苯巴比妥对 S(+ ) -和 R(-) -普罗帕酮 (PPF)体外 相代谢有无立体选择性的影响。方法 :将消旋普罗帕酮与对照或苯巴比妥诱导的大鼠肝微粒体孵育后 ,采用手性衍生化反相高效液相色谱法 ,测定对映体的经时孵育曲线和酶动力学参数 (最大反应速度、米氏常数、内在清除率 )。结果 :在对照大鼠肝微粒体中 ,PPF的 相代谢无立体选择性。经苯巴比妥诱导处理后 ,在 5mg/ L 底物浓度时 R(-) -PPF的代谢快于 S(+ ) -PPF,两对映体的米氏常数和内在清除率有显著性差异。结论 :苯巴比妥选择性地诱导了大鼠肝微粒体对 PPF的

Objective:To investigate whether phenobarbital (PB) stereoselectively induces phase Ⅰ metabolism of propafenone(PPF) in rat liver microsome.Methods:The curves of reaction time vs. concentration of each enantiomer and the parameters of enzymatic kinetics for both enantiomers were determined by using a chiral reverse phase high performance liquid chromatography after incubation of racemic PPF with control or PB pretreated rat liver microsome.Results:The depletion of R(-) PPF was faster than that of S(+) PPF at 5 mg/L of substrate concentration in PB pretreated rat liver microsome incubates. Enantiomeric differences in K m and Cl int were both significant. However, no stereoselectivity was observed in controls.Conclusion:PB stereoselectively induces phase Ⅰ metabolism of propafenone in rat liver microsome.