儿童癫痫患者奥卡西平群体药动学模型验证  

Evaluation of the population pharmacokinetic models of oxcarbazepine in pediatric patients with epilepsy

作　　者：李瑞瑞[1] 盛晓燕[1] 马凌悦[1] 许俊羽[1] 赵侠[1] 周颖[1] 崔一民[1] 

机构地区：[1]北京大学第一医院药剂科,北京100034

出　　处：《中国新药杂志》2016年第6期668-673,共6页Chinese Journal of New Drugs

基　　金：首都临床特色应用研究与成果推广项目(Z15110000-4015044)

摘　　要：目的：根据模型拟合图形,判断儿童癫痫患者奥卡西平群体药动学模型对中国癫痫患儿血药浓度数据的拟合效果,探讨已发表模型对不同临床机构的适用性,选择适合中国患儿的群体药动学模型。方法：本研究统计分析了已发表的关于癫痫儿童的奥卡西平活性代谢物10-羟基卡马西平群体药动学模型,并提取了已发表文献中的人口学信息及模型信息,将我院癫痫患儿的浓度数据进行模型拟合,根据实测浓度-预测浓度（DV-PRED）图及可视化预测检验（VPC）评估拟合效果。结果：本研究共收集到我院69例癫痫患儿的76个稳态谷浓度点,入组患儿的年龄范围为0.17~15岁;共检索到7篇奥卡西平的群体模型,对其中5篇进行拟合,其中模型A和D的拟合效果较好。结论：仍需建立适合中国癫痫患儿的奥卡西平群体模型。Objective： To analyze the published population pharmacokinetic models,and investigate the transferability of published models to different clinical settings,and finally select the appropriate population pharmacokinetic models special for Chinese pediatric patients according to the stimulation performance. Methods： We analyzed the published population pharmacokinetic models of monohydroxycarbazepine,an active oxcarbazepine metabolite,and extracted the patient demographics and model information from those models. The simulation performance was evaluated by the observed concentration-predicted concentration graph（ DV-PRED graph） and Visual Predictive Checks（ VPC）. Results： We measured concentrations of monohydroxycarbazepine from 76 blood samples of 69 epileptic pediatric patients. The age of the patients varied from 0. 17 to 15 years old. We searched 7population pharmacokinetics of oxcarbazepine and stimulated 5 population pharmacokinetic models,and finally model A and model D did a better performance. Conclusion： It is necessary to reestablish the population pharmacokinetic models of oxcarbazepine in pediatrics.

关 键 词：奥卡西平 10-羟基卡马西平 外部验证 群体药动学 儿童 癫痫 

分 类 号：R969.1[医药卫生—药理学]