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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 相代谢
Objective: To observe the effect of phenobarbital on the stereoselectivity of S (+) - and R (-) - propafenone (PPF) in vitro. Methods: After incubation of racemic propafenone with control or phenobarbital-induced rat liver microsomes, chiral derivatization reversed-phase high performance liquid chromatography (RP-HPLC) was used to determine the enantiomeric growth curves and enzyme kinetics Learning parameters (maximum response rate, Michaelis constant, intrinsic clearance). Results: There was no stereoselectivity in the phase metabolism of PPF in control rat liver microsomes. After phenobarbital induction, R (-) - PPF was metabolized faster than S (+) - PPF at a substrate concentration of 5 mg / L, and the Michaelis constants and intrinsic clearance of the two enantiomers were significantly different . CONCLUSION: Phenobarbital selectively induces the phase metabolism of PPF in rat liver microsomes