用非线性混合效应模型法建立癫痫儿童拉莫三嗪的群体药代动力学模型

发布时间：2018-01-27 00:12

本文关键词： 拉莫三嗪癫痫群体药代动力学非线性混合效应模型法　出处：《中国临床药理学杂志》2016年17期 　论文类型：期刊论文

【摘要】：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。
[Abstract]:Objective to establish a population pharmacokinetic model of lamotrigine in epileptic children by nonlinear mixed effect model (NONMEM). Methods 140 epileptic children who took lamotrigine were retrospectively collected. Blood concentration data and clinical data were collected from 165 patients aged 16 years. The serum drug concentration was the steady-state concentration of clinical routine monitoring. The pharmacokinetic model of children with epilepsy was established by NONMEM and software. The accuracy of the model parameters was evaluated by bootstrap method and normal predictive distribution error (NPDE). The final regression model established was the total body clearance rate (CLP / FG) 1.60 脳 WTP / 40). 0.79 脳 etrocardia (-1.25 脳 TAMT1 / 500) 脳 4.25 (CBZ). Distributed volume V / F = 330 脳 TAMTR / 100 / 5. 26 脳 0.1 / L CLP / F. The population typical values of V / F were 1.60 L 路hl-1 and 330L respectively. Conclusion the pharmacokinetic model of lamotrigine in epileptic children was established by NONMEM method. It can be used to predict blood drug concentration.
【作者单位】：中国医科大学附属盛京医院药学部;
【基金】：国家自然科学基金资助项目(81302857) 辽宁省自然科学基金资助项目(2013021079)
【分类号】：R969.1
【正文快照】： (中国医科大学附属盛京医院药学部,沈阳110004)CHEN Ya-nan,QIU Feng,XU Shan-sen,ZHANG Ti,YANG Fan,ZHAO Li-mei(Shengjing Hospital of China MedicalUniversity,Shenyang 110004,China)拉莫三嗪(LTG)是新一代抗癫痫药物(AEDs),广泛应用于部分性发作、全面性发作以及双相情

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