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目的建立酒石酸唑吡坦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。方法选择汉、蒙、朝、维4个民族各10名(男、女各5)、回族9名(男5女4)健康志愿者,口服酒石酸唑吡坦片10 mg后测定血药浓度,用非线性混合效应模型(NONMEM)程序建立酒石酸唑吡坦的群体药动学模型,并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带有滞后时间的一室模型为结构模型,药动学参数CL/F、V/F和Ka的群体典型值及其相对标准误差分别为23.1 L.h-1(7.58%)、53.0 L(5.11%)和5.07 h-1(13.6%)。同时性别和民族因素对清除率有显著影响(P<0.001),民族因素对表观分布容积有显著影响(P<0.001)。结论用NONMEM软件拟合建立的酒石酸唑吡坦群体药动学模型,经验证稳定可靠。
OBJECTIVE: To establish a population pharmacokinetic model of zolpidem tartrate in different ethnic groups in China, and to provide a reference for clinical individualized administration. Methods A total of 10 healthy volunteers (Han, Mongol, North Korea and North Korea), 10 males and 5 females, and 9 Hui women (4 males and 4 females) were enrolled. Oral administration of 10 mg zolpidem tartrate tablets The population pharmacokinetic model of zolpidem tartrate was established by nonlinear mixed effect model (NONMEM) program. The effects of demographic, biochemical and other related factors on the pharmacokinetic parameters were also investigated and the model was validated. Results One compartment model with lag time, which was absorbed and eliminated by first order, was selected as the structural model. The typical population of CL / F, V / F and Ka populations and their relative standard errors were 23.1 Lh-1 (7.58 %), 53.0 L (5.11%) and 5.07 h-1 (13.6%). At the same time, the gender and ethnic factors had a significant effect on the clearance rate (P <0.001), while the ethnic factors had a significant effect on the apparent volume of distribution (P <0.001). Conclusion The pharmacokinetic model of zolpidem tartrate fits established by NONMEM software has been proved to be stable and reliable.