替硝唑在中国不同民族健康志愿者中的群体药动学研究

 目的建立替硝唑在中国不同民族中的群体药动学模型,为临床个体化给药提供参考。方法用群体药动学方法,对50名汉、蒙、朝、回、维族健康志愿者的血药浓度进行分析,用非线性混合效应模型(NONMEM)程序建立替硝唑的群体药动学模型,考察人口统计学指标、生化指标等相关因素对药动学参数的影响,并进行模型验证。结果选择一级吸收和消除的二室模型为结构模型,药动学参数CL₁,CL₂,V₁,V₂和Ka的群体典型值及其相对标准误差分别为0.807L·h^-1(10.7%),205L·h^-1(9.32%),3.29L(17.7%),19.0L(15.4%)和1.51h^-1(8.28%)。同时民族和体重对中央隔室清除率有显著影响(P<0.001),民族和性别对中央隔室表观分布容积有显著影响(P<0.001),体重对外周隔室表观分布容积有显著影响(P<0.001)。结论用NONMEM软件拟合建立的替硝唑群体药动学模型,经验证稳定可靠。

Population Pharmacokinetics of Tinidazole in Five Different Ethnic Populations of China

OBJECTIVE To construct the population pharmacokinetic(PPK) model of tinidazole in five major ethnic populations in China for individualized drug therapy in clinical practice.METHODS The population pharmacokinetic model of tinidazole was developed for 50 healthy subjects from Han,Mongol,Korean,Hui and Uighur nationality,the major 5 nationalities of China after oral administration.The effects of demography and biochemical covariates were investigated by NONMEM.Internal and external validations were conducted for the model.RESULTS A two-compartment model with first-order absorption and elimination process was confirmed as structure model of tinidazole.The population typical values and relative standard errors(RSE) of CL₁,CL₂,V₁,V₂ and Ka were 0.807(10.7%)L·h^-1,205(9.32%)L·h^-1,3.29(17.7%)L,19.0(15.4%)L and 1.51(8.28%) h^-1 respectively.The result showed that race and body weight covariates showed significant influence on CL₁(P<0.001).Race and gender covariates showed significant influence on V₁(P<0.001).Body weight covariate showed significant influence on V₂(P<0.001).CONCLUSION The final PPK model of tinidazole in for 5 major Chinese nationalityies was established by NONMEM.The PPK model was steady and reliable.