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目的:考察维拉帕米(VPM)和去甲维拉帕米(NVPM)对映体的药代动力学特性。方法:8名汉族男性健康志愿者分别po外消旋VPM80mg和静滴5mg,以三甲基β环糊精为手性选择剂,毛细管电泳法同时测定VPM和NVPM对映体的血浆浓度,用二房室开放模型拟合药时曲线。结果:poVPM的R/S(AUC),R/S(CL)和R/S(Cmax)比率分别为366±186,03±0053和482±058;NVPM的R/S(Cmax)和R/S(AUC)比率为258和236。ivVPM的R/S(AUC),R/S(CL)和R/S(Cmax)比率分别为104±029,101±03和136±012。R(+)VPM和S(-)VPM的绝对生物利用度为303±19和98±59。结论:VPM有较大的对映体特异性首过代谢,选择优对映体S(-)VPM为监测对象有利于临床合理使用外消旋VPM。
OBJECTIVE: To investigate the pharmacokinetics of enantiomers of verapamil (VPM) and norvirabepam (NVPM). Methods: Eight male Han volunteers were treated with VP racemic VPM 80mg and intravenous drip 5mg respectively. The plasma concentrations of VPM and NVPM enantiomers were determined by capillary electrophoresis with trimethylβcyclodextrin as chiral selector , With a two-bedroom open model to fit the drug curve. Results: The ratios of R / S (AUC), R / S (CL) and R / S (Cmax) were 366 ± 186, 03 ± 0053 and 482 ± 058 ; NVPM R / S (Cmax) and R / S (AUC) ratio of 2 58 and 2 36. The ratios of R / S (AUC), R / S (CL) and R / S (Cmax) of ivVPM were 104 ± 029,101 ± 03 and 136 ± 012, respectively. The absolute bioavailability of R (+) PMM and S (-) PMM was 303 ± 19 and 98 ± 59. CONCLUSION: VPM has larger enantioselective first-pass metabolism. Selecting the superior enantiomer S (-) PMM as the monitoring target is helpful for the clinical rational use of racemic VPM.