盐酸米那普仑在中国健康人体中的群体药代动力学研究

发布时间：2018-04-17 16:54

本文选题：盐酸米那普仑 + 群体药代动力学模型　；参考：《中国临床药理学杂志》2017年04期

【摘要】：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。
[Abstract]:Objective to evaluate the pharmacokinetic characteristics and possible influencing factors of minapram hydrochloride in Chinese healthy population.Methods A total of 12 subjects (male and female) were treated with a single dose of 2550mg Latin square triple crossover self-control design.The elution period of each drug cycle was 7 days, and 12 subjects (male and female) in multiple administration group were given drugs for 8 days (titrated to 100 mg / d, 50 mg / d).The plasma concentration of minapram hydrochloride was determined by HPLC-MS / MS, and the population pharmacokinetic parameters were obtained by using NONMEN (a nonlinear mixed effect model).Results the pharmacokinetic parameters of the model were estimated to be 95% confidence interval (95% confidence interval). The results showed that the clearance rate (CLL) was 37.53 ~ 44.16 ~ (-1) L ~ (-1), the apparent distribution volume (V) was 382.89 ~ (43) ~ (3.37) ~ 408.13 卤12.86 L, and the absorption constant was 0.811 ~ (1.31) 卤0.13 ~ (-1) 路h. Gender and body weight had no effect on the clearance of minapram hydrochloride.Conclusion the model is stable and can fit the population pharmacokinetic characteristics of minapram hydrochloride.
【作者单位】：首都医科大学附属北京安定医院临床精神药理实验室及北京市精神疾病诊断与治疗重点实验室;首都医科大学附属北京儿童医院药学部;首都医科大学附属北京安定医院精神病学系精神疾病诊断与治疗北京市重点实验室北京脑重大疾病研究精神分裂症研究所;
【基金】：首都卫生发展专项基金资助项目(2014-2-2122) 首都临床特色应用研究与成果推广项基金资助项目(z15110000401580) 北京市医院管理局临床医学发展专项基金资助项目(ZYLX201403)
【分类号】：R969.1

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