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:采用对照及 β-萘黄酮 (β- NF)或地塞米松(Dex)诱导的大鼠肝微粒体 ,应用 GITC柱前衍生化 ,反相高效液相色谱法研究了消旋普罗帕酮〔(R/S) - PPF〕体外代谢的立体选择性 .实验结果表明 ,在 Dex,β- NF诱导的微粒体中有 N-去丙基普罗帕酮生成。在 β- NF,Dex预处理组 ,(R/S) - PPF低浓度时的经肝微粒体代谢具有立体选择性 ,R(- )对映体的清除大于 S(+)对映体 ,高浓度时的代谢无立体选择性 .R(- )对映体的 Km 值显著低于 S(+)对映体 ,而 Vmax值无显著性差异 .在 Dex预处理组中的立体选择性大于 β- NF组 .在对照组中代谢无立体选择性 ,且 Km,Vmax值均小于β- NF,Dex预处理组。结果提示 ,CYP1 A,CYP3A4亚族对普罗帕酮 (PPF)的 N-去丙基化有贡献 .(R/S) - PPF的N-去丙基化具有浓度依赖性的立体选择性
: Rat liver microsomes induced by β-naphthoflavone (β-NF) and dexamethasone (Dex) were isolated and purified by GITC precolumn derivatization and reversed-phase high performance liquid chromatography (R / S) - PPF] in vivo.Experimental results show that N-propylpropafenone is produced in Dex, β-NF-induced microsomes. In the β-NF, Dex preconditioning and (R / S) -PPF low concentration, the metabolism of hepatic microsome was stereoselective. The R (-) enantiomer clearance was larger than that of the S (+) enantiomer, There was no stereoselectivity for the metabolites at the concentration of 0. The Km values of the R (-) enantiomer were significantly lower than those of the S (+) enantiomer, with no significant difference in Vmax values. The stereoselectivity in the Dex pretreatment group was greater than that in the β - NF group in the control group in the absence of stereospecific metabolism, and Km, Vmax values were less than β-NF, Dex pretreatment group. The results suggest that the CYP1 A and CYP3A4 subfamilies contribute to N-desylation of propafenone (PPF). N-des-propylation of (R / S) -PPF has a concentration-dependent stereoselectivity