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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。
OBJECTIVE To establish a population pharmacokinetic model of flupirtine based on blood concentration data of oral flupirtine in 5 ethnic subjects so as to achieve individualized medication. Methods Ten healthy subjects (half male and half female) in each of Han, Mongol, North Korea and Uyghur nationality were enrolled. 588 plasma samples collected after administration were tested for the content of flupirtine by HPLC-fluorescence method. The effects model software computes the underlying and final models as well as the population pharmacokinetic parameters; demographics and biochemical indicators as covariates. Results The basic model of flupirtine was a one-compartment model. The typical pharmacokinetic parameters 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%). The influence of ethnic factors on the pharmacokinetic parameters CL / F, V / F and Ka was significant, while the gender factors had a significant effect on CL / F and Ka. Conclusion The final population pharmacokinetic model of flupirtine was established by NONMEM method. The model is stable and reliable. The results of the population pharmacokinetic analysis show that ethnic and gender factors have a significant effect on the pharmacokinetic behavior in healthy subjects.