反式曲马朵及其活性代谢物氧去甲基曲马朵对映体的血浆蛋白结合

Plasma Protein Binding of the Enantiomers of trans Tramadol and Its Active Metabolite, O-Demethyltramadol

目的 研究反式曲马朵 (transT)及其活性代谢物氧去甲基曲马朵 (M1)对映体的血浆蛋白结合。方法 大鼠腹腔注射单剂量盐酸transT ,1h后取血 ,离心超滤法制备血浆超滤液 ,高效毛细管电泳法测定血浆及其超滤液中transT和M1对映体的浓度 ,配对 t-检验比较对映体间的浓度与血浆蛋白结合率。结果 血浆中 (+) - transT的总浓度和游离浓度均高于(- ) -transT ,(+) -transT的血浆蛋白结合率低于 (- ) -transT。M1两对映体的总浓度、游离浓度和血浆蛋白结合率无明显区别。结论 transT与血浆蛋白结合具有立体选择性 。

Aim To study the plasma protein binding of the enantiomers of trans tramadol (trans T) and its active metabolite, O-demethyltramadol (M 1). Methods Blood samples were taken 1h after a single ip dose of trans T hydrochloride. The ultrafiltrate of plasma was gotten by centrifugation with means of a Microcon centrifugal filter device. The concent rations of the enantiomers of trans T and M 1 in plasma and its ultrafiltrate were determined by high performance capillary electrophoresis (HPCE). The concentrations and plasma protein binding ratio between the two enantiomers of trans T and M 1 were compared through paired t-test. Results The total and free concentrations of (+)-trans T were higher than those of (-)-trans T; But the plasma protein binding ratio of (+)-trans T were lower than that of (-)-trans T. Between the two enantiomers of M 1, there were no significant differences in total concentrations, free concentrations and plasma protein binding ratio. Conclusion The plasma protein binding of trans T showed marked stereoselectivity. While the plasma protein binding of M 1 didn't exhibit obvious stereoselectivity.