应用NLME程序建立丙戊酸在中国癫痫患儿中的群体药动学模型

发布时间：2018-06-30 18:24

本文选题：癫痫 + 儿童　；参考：《中国医院药学杂志》2015年14期

【摘要】：目的:建立中国癫痫患儿口服丙戊酸的群体药动学模型,促进合理用药。方法:收集472例癫痫患儿口服丙戊酸后的血药浓度数据和临床资料。将患儿随机分成2组,PPK模型组(n=354):应用NLME程序建立一房室群体药动学模型(个体间变异采用指数模型,残差变异采用加法模型表示),考察各协变量对参数Ka、Vd和Cl的影响。用拟合优度、自举验证、直观预测检验(VPC)对最终模型的性能进行内部验证。PPK验证组(n=118):用最终模型预测验证组患儿的血药浓度,与实测值比较计算平均预测误差(MPE)、平均绝对预测误差(MAE)、平均预测误差平方(MSE)和均方根预测误差(RMSE)对最终模型进行外部验证。结果:PPK最终模型为:Ka=1.18×eηKa h-1;Vd=0.30×eηVd L·kg-1;Cl=0.008×(WT/18)-0.92×eηCl L·kg-1·h-1。体质量负相关影响Cl。拟合优度、自举验证和VPC的评价结果表明最终模型稳定、预测结果可靠。外部验证最终模型结果为:MPE=-0.09 mg·L-1,MAE=0.72 mg·L-1,MSE=0.76(mg·L-1)2,RMSE=0.87 mg·L-1。血药浓度实测值和最终模型的个体预测值(DV vs IPRED)的决定系数R2=0.998 1。外部验证说明最终模型预测准确度高。结论:本研究成功建立了中国癫痫患儿口服丙戊酸后的群体药动学模型。模型结构表明丙戊酸体重校正的清除率随患儿年龄和体质量的增加有下降趋势。
[Abstract]:Objective: to establish a group pharmacokinetic model of valproic acid in epileptic children in China and to promote rational use of valproic acid. Methods: blood concentration data and clinical data of 472 epileptic children after oral valproic acid were collected. The children were randomly divided into two groups: the NLME program was used to establish a pharmacokinetic model of atrioventricular population (the inter-individual variation was exponential model, the residual variation was expressed by the additive model), and the influence of each covariable on the parameters Kav Vd and Cl was investigated. Internal validation of the performance of the final model with goodness of fit, bootstrap verification, visual prediction test (VPC). PPK validation group (nnb118): the final model was used to predict the blood drug concentration of the children in the validation group. The calculated mean prediction error (MPE), mean absolute prediction error (mae), mean prediction error square (MSE) and root-mean-square prediction error (RMSE) were compared with the measured values to verify the final model. Results the final model of 1. 18 脳 e 畏-Ka-h-1 kg-1 is: 0. 30 脳 e 畏 Vd L kg-1 Cln 0.008 脳 (WT18) -0. 92 脳 e 畏 Cl L kg-1 h-1. The negative correlation of body mass affects Cl. The results of goodness of fit, bootstrap verification and VPC evaluation show that the final model is stable and the prediction results are reliable. The result of external verification is as follows: MPE-0.09 mg / L MAEN 0.72 mg / L ~ (-1) MSE _ (0.76) (mg ~ (-1) ~ (2) RMSE ~ (-1) 0.87 mg / L ~ (-1). The determinant coefficient of DV vs IPRED was R20.998 1, the measured value of blood drug concentration and the individual predictive value (DV vs IPRED) of the final model. External verification shows that the prediction accuracy of the final model is high. Conclusion: this study successfully established a population pharmacokinetic model of Chinese children with epilepsy after oral valproic acid. The model structure showed that the clearance rate of valproic acid weight correction tended to decrease with the increase of age and body mass.
【作者单位】：武汉市儿童医院;
【分类号】：R969.1

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