基于群体药动学的奥卡西平儿童个体化给药模式的建立  

A clinical application mode of oxcarbazepine dosage regimen individualization for children with epilepsy based on population pharmacokinetics

作　　者：汪洋[1] 张华年[1] 陈渝军[1] 徐华[1] 许琼[1] 高萍[1] 刘茂昌[1] 

机构地区：[1]武汉市儿童医院,湖北武汉430016

出　　处：《中国新药与临床杂志》2016年第3期210-215,共6页Chinese Journal of New Drugs and Clinical Remedies

基　　金：2014年度武汉市临床医学科研项目(WX14C47)

摘　　要：目的基于群体药动学(PPK)和贝叶斯原理,建立奥卡西平的癫痫患儿个体化给药工作模式,促进临床合理用药。方法利用已发表的中国癫痫患儿口服奥卡西平后的PPK模型和JPKD-Bayesian软件建立奥卡西平个体化给药的预测模型。运用该模型对100例癫痫患儿进行个体化给药方案设计。患儿按设计方案规律服药2~4周后测定10-羟基卡马西平的稳态血清谷浓度并与模型预测值相比较,计算平均预测误差、平均绝对预测误差、平均相对预测误差、相对预测误差在±20%和±30%内的比例来验证模型的预测性能。结果个体化给药预测模型的平均预测误差为(0.54±2.00)mg·L^(-1),平均绝对预测误差为(1.75±1.09)mg·L^(-1),平均相对预测误差为(3.86±14.56)%,其中分别有78%和96%的血药浓度数据相对预测误差在±20%和±30%以内。血药浓度预测值对实测值的决定系数R2=87.8%。上述验证结果说明模型的预测准确度和精密度均较高。结论本研究成功建立了可用于儿科患者实施奥卡西平个体化给药的预测模型和完整的工作模式,有助于临床合理用药。AIM To establish a clinical application mode of oxcarbazepine （Oxc） dosage regimen individualization for children with epilepsy based on population pharmacokinetics （PPK） and Bayesian method, and to optimize rational use of Oxc. METHODS A predictive model for individualization of Oxc dosage regimen was established based on the JPKD- Bayesian software and a published PPK model of Oxc oral application in Chinese children with epilepsy. Individual dosage regimens of Oxc were devised for 100 cases of pediatric patients by using the predictive model. The trough concentrations of steady state 10- hydroxycarbazepine were measured after the patients taking Oxc for 2 - 4 weeks according to individual dosage regimens, and which were compared with the predictive concentrations obtained from model. The mean predicted error, mean absolute prediction error, mean relative prediction error and the individual ratio of relative prediction error within ＋ 20% and ＋ 30% were calculated to assess the predictive model. RESULTS The mean predicted error of the established model for Oxc dosage regimen individualization was （0.54 ±2.00） mg .L-1, mean absolute prediction error was （ 1.75 ± 1.09） mg-L-1, and mean relative prediction error was （3.86 ± 14.56） %. There were 78% and 96% of relative prediction error within ±20% and ＋30%, respectively. The determination coefficient of predicted value-observations was 87.8%. The predictive accuracy and precision of the model were accepted by above evaluation results. CONCLUSION A predictive model and its clinical application mode for individualization of Oxc dosage regimen in children was established in this study, which will be useful for optimizing rational use of Oxc.

关 键 词：奥卡西平 10-羟基卡马西平 群体药动学 贝叶斯法 儿童 个体化给药 

分 类 号：R969.1[医药卫生—药理学]