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目的评价盐酸米那普仑在中国健康人群的群体药代动力学特征及可能的影响因素。方法单次给药共有12例受试者(男女各半),进行3个剂量组(25,50,100 mg)的拉丁方三交叉自身对照设计,每个服药周期洗脱期为7 d;多次给药组12例受试者(男女各半),连续8 d给药(给药剂量滴定至每天100 mg,每次50 mg)。液质联用法(HPLC-MS/MS)测定盐酸米那普仑的血浆浓度,以非线性混合效应模型(NONMEN)进行分析,获得群体药代动力学参数。结果最终模型为Ⅰ室模型,模型的药代动力学参数估计值(95%置信区间)分别为:清除率(CL)为37.53~44.16(40.84±1.69)L·h~(-1),表观分布容积(V)为382.89~433.37(408.13±12.86)L,吸收常数(Ka)为0.81~1.31(1.06±0.13)/h,性别和体重对盐酸米那普仑的清除无影响。结论本模型稳定,能较好的拟合盐酸米那普仑的群体药代动力学特征。
Objective To evaluate the population pharmacokinetic characteristics and possible influencing factors of milnacipran hydrochloride in Chinese healthy population. Methods A total of 12 subjects (half-males and half-females) received a single dose of latin-3-crossover self-control study in three dose groups (25, 50 and 100 mg) Twelve subjects (half-males and half-females) in the dosing group were dosed for 8 consecutive days (titrated to 100 mg daily, 50 mg each time). The concentration of milnacipran hydrochloride in plasma was determined by liquid chromatography-mass spectrometry (HPLC-MS / MS) and the nonlinear pharmacokinetic parameters of the population were obtained by nonlinear mixed effect model (NONMEN). Results The final model was model Ⅰ. The estimated pharmacokinetic parameters (95% confidence intervals) of the model were: clearance (CL) 37.53 ~ 44.16 (40.84 ± 1.69) L · h -1 The distribution volume (V) was 382.89 ~ 433.37 (408.13 ± 12.86) L, and the absorption constant (Ka) was 0.81 ~ 1.31 (1.06 ± 0.13) / h. Gender and body weight had no effect on the clearance of milnacipril hydrochloride. Conclusion This model is stable and can fit the population pharmacokinetic characteristics of milnacipran hydrochloride.