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目的用非线性混合效应模型(NONMEM)方法建立拉莫三嗪在癫痫儿童中的群体药代动力学模型。方法回顾性收集140例服用拉莫三嗪的癫痫患儿(1~16岁)的165份血药浓度数据及临床资料。血药浓度为临床常规监测的稳态浓度,用高效液相色谱法测定。用NONMEM及辅助软件建立癫痫儿童的群体药代动力学模型,用自举法和正态化预测分布误差(NPDE)评估模型参数的精确度。结果建立的最终回归模型为全身清除率(CL/F)=1.60×(WT/40)0.79×e~(-1.25×TAMT1/500)×4.25~(CBZ),分布容积(V/F)=330×(TAMT/100)~(5.26×0.1),CL/F、V/F的群体典型值分别为1.60 L·h~(-1)和330 L。结论用NONMEM法初步建立了拉莫三嗪在癫痫儿童的群体药代动力学模型,可用于预测血药浓度。
Objective To establish a population pharmacokinetic model of lamotrigine in children with epilepsy by nonlinear mixed effect model (NONMEM). Methods The data of 165 plasma concentrations and clinical data of 140 children with epilepsy (1 ~ 16 years old) taking lamotrigine were retrospectively collected. Plasma concentration is the steady-state concentration routinely monitored in the clinic and determined by high performance liquid chromatography. A population pharmacokinetic model was established for children with epilepsy using NONMEM and aided software. Bootstrap method and Normalized Prediction Distribution Error (NPDE) were used to evaluate the accuracy of model parameters. Results The final regression model was established as a whole body clearance rate (CL / F) = 1.60 × (WT / 40) 0.79 × e -1.25 × TAMT1 / 500 × 4.25 CBZ and V / F = 330 TAMT / 100 to 5.26 × 0.1, and the typical CL / F and V / F populations were 1.60 L · h -1 and 330 L, respectively. Conclusion The population pharmacokinetic model of lamotrigine in children with epilepsy was preliminarily established by NONMEM method and could be used to predict the plasma concentration.