氟吡汀在中国多民族健康受试者体内的群体药动学研究(英文)  

Population pharmacokinetics of flupirtine in Chinese healthy volunteers of different nationalities

作　　者：郭涛[1] 赵龙山[2] 刘龙兴[2] 杨璐[2] 李新刚[3] 夏东亚[1] 毕姗姗[3] 卢玮[3] 

机构地区：[1]沈阳军区总医院药剂科,沈阳110016 [2]沈阳药科大学药学院,沈阳110016 [3]北京大学药学院,北京100034

出　　处：《中国临床药学杂志》2014年第5期270-275,共6页Chinese Journal of Clinical Pharmacy

摘　　要：目的根据5个民族受试者口服氟吡汀后的血药浓度数据建立氟吡汀的群体药动学模型,从而实现个体化用药。方法选择汉、蒙、朝、维和回族各10名健康受试者(男女各半),将给药后收集到的588份血浆样品采用HPLC-荧光法测定氟吡汀的含量,采用非线性混合效应模型软件计算基础模型和最终模型以及群体药动学参数;人口统计学和生化指标因素作为协变量来进行考察。结果氟吡汀的基础模型为一室模型,群体药动学参数CL/F、V/F和Ka的典型值和相对标准误(RSE%)分别为11.6 L·h-1(3.04%)、116 L(4.50%)和3.03 h-1(14.8%)。民族因素对药动学参数CL/F、V/F和Ka影响较为显著,而性别因素对CL/F和Ka影响较为显著。结论用NONMEM法建立了氟吡汀5个民族的最终群体药动学模型。该模型稳定可靠。群体药动学分析结果表明,民族和性别因素对于健康受试者体内的药动学行为具有显著影响。AIM To establish a population pharmacokinetic （PPK） model of flupirtine based on data from five Chinese ethnicities, so as to adjust individual administration. METHODS Ten healthy subjects （5 male, 5 female） of each ethnicity including Han, Mongolian, Korean, Uigur and Hui were involved. All 588 plasma concentrations of flupirtine were determined by HPLC-fluoreseence （FLU）. Basic models and final models of flupirtine were developed by nonlinear mixed-effects modeling （NONMEM） software and PPK parameters were acquired. The effects of demography and biochemical eovariates were investigated. RESULTS The basic pharmacokinetics of flupirtine was described by one- compartment pharmaeokinetie model. The population typical values and relative standard errors （RSE % ） of CL/F, V/ F and Ka were 11.6 L·h^-1（3.04%）, 116 L （4.50%） and 3.03 h^-1（14.8%）, respectively. Ethnieity showed sig- nificant influence on CL/F, V/F and Ka （P 〈 0.001）. Sex showed significant effect on CL/F and Ka （P 〈 0.001）. CONCLUSION The final PPK model of flupirtine in 5 major Chinese ethnieities is established by NONMEM. The PPK model is proved to be reliable. PPK analysis pointed that ethnieity and sex have significant impact on the pharmaeokinetits of flupirtine in healthy volunteers.

关 键 词：氟吡汀 群体药动学 NONMEM 民族 性别 

分 类 号：R96[医药卫生—药理学]