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目的:研究反式曲马朵[(±)一trans-T]代谢及反式氧去甲基曲马朵(M1)生成的立体选择性,方法:(±)-trans-T及其对映体分别与大鼠肝微粒体孵育,高效毛细管电泳法测定孵育液中(±)-trans-T及M1对映体的浓度。结果:以(±)-trans-T单一对映体为底物孵育时,(+)-trans-T的代谢速率较低,(+)-M1生成有较低的V_(max)和CL_(int).以(±)-trans-T消旋体为底物孵育时,(±)-trans-T对映体的代谢速率及(±)-M1对映体的生成速率不同程度地减慢。右美沙芬、普罗帕酮和氟西汀既能抑制(±)-trans-T的代谢,又能抑制M1的生成;普罗帕酮和氟西汀能增强(±)-trans-T代谢及M1生成的立体选择性,右美沙芬仅使M1生成的立体选择性增强。结论:在大鼠肝微粒体中,(±)-trans-T代谢及M1生成有立体选择;(±)-trans-T对映体间存在相互作用。右美沙芬、普罗帕酮及氟西汀对它们的立体选择性产生不同的影响。
OBJECTIVE: To study the stereoselectivity of trans (±) trans-T trans and trans-O-demethylation of tramadol (M1). METHODS: The (±) -trans-T and its enantiomer The rat liver microsomes were incubated with high performance capillary electrophoresis. The concentrations of (±) -trans-T and M1 enantiomers in the incubation solution were determined. RESULTS: The (+) - trans-T had a lower metabolic rate when incubated with the (±) -trans-T single enantiomer as a substrate, lower V max and CL_ int). The (±) -trans-T enantiomer metabolic rate and (±) -M1 enantiomer production rate slowed to some extent when incubated with (±) -trans-T racemate . Dextromethorphan, propafenone and fluoxetine not only inhibited the metabolism of (±) -trans-T but also inhibited the production of M1; propafenone and fluoxetine enhanced (±) -trans-T metabolism and M1 The stereoselectivity generated, dextromethorphan, only makes the stereospecificity of M1 enhanced. CONCLUSION: There is a stereoselective (±) -trans-T metabolism and M1 production in rat liver microsomes; there is an interaction between (±) -trans-T enantiomers. Dextromethorphan, propafenone and fluoxetine have different effects on their stereoselectivity.