建立中国癫痫儿童丙戊酸钠的群体药动学/药效学结合模型  

Population pharmacokinetic/pharmacodynamic modeling of valproate in Chinese children with epilepsy

作　　者：姜德春 王丽 王育琴 卢炜 白向荣 

机构地区：[1]Department of Pharmacy, Xuan-wu Hospital, Capital Medical University [2]Department of Pediatrics, First Hospital, Peking University, Beijing 100083, China [3]Department of Pediatrics, First Hospital, Peking University [4]Department of Pharmaceutics, School of Pharmaceutical Science, Peking University [5]State Key Lab. of Natural and Biomimetic Drugs, Beijing 100083, China

出　　处：《中国临床药理学与治疗学》2007年第10期1179-1180,共2页Chinese Journal of Clinical Pharmacology and Therapeutics

摘　　要：AIM: To establish a population pharmacokinetic/pharmacodynamic (PK/PD) model for valproate (VPA) in children with epilepsy in China, and promote reasonable use of antiepileptic drug in clinical practice. METHODS: Sparse data of VPA serum concentrations from 417 pediatric children were collected. These patients were divided into three groups: Population PK-Index group, n=317; Population PK-Valid group, n=100; 115 of the total 417 subjects were also included in the Population PD group. Population PK parameters of VPA were estimated based on the data from population PK-Index group. In the validation procedure, the serum concentrations of VPA from the population PK-Valid group were predicted by base and final models respectively. To assess the accuracy and precision of the predictions, mean prediction error (MPE), mean squared prediction error (MSPE), root mean squared prediction error (RMSPE), weight-residues (WRES) and its 95% confidence intervals (95%CI) were all calculated, then compared between the two models. For population PD group, all of the 115 patients were VPA monotherapy. Efficacy of epilepsy treatment was divided into 5 grades according to the percentage of seizure frequency decreased (PSFD%). The value of PSFD% 100%, 75%-100%, 50%-75%, 25%-50%, or less than 25% are corresponding to grade 1 to 5. For population PD group, the quantitative relationship between the VPA serum concentrations and the probability for its efficacy score was characterized by logistic regression. RESULTS: Population PK of VPA was described by one-compartment model with first order absorption. In the final model, Ka, V/F, CL/F are 0.251+2.24·(1-HS) (/h), 2.88+0.157·WT (L), 0.1060.98·CO+0.0157·AGE (L/h), respectively. The final model was validated internally and externally. Logistic regression showed that VPA serum concentrations and corresponding peak probability for its efficacy were (25 μg/mL, grade 5, 50%), (32 μg/mL, grade 4, 32.3%), (50 μg/mL, grade 3, 26.3%), (67 μg/mL, grade 2, 36.5%), and (78 μg/mL, grade 1, 50%),AIM： To establish a population pharmacokinetic/pharmacodynamic （PK/PD） model for valproate （VPA） in children with epilepsy in China, and promote reasonable use of antiepileptic drug in clinical practice. METHODS： Sparse data of VPA serum concentrations from 417 pediatric children were collected. These patients were divided into three groups： Population PK-Index group, n = 317; Population PK-Valid group, n = 100; 115 of the total 417 subjects were also included in the Population PD group. Population PK parameters of VPA were estimated based on the data from population PK-Index group. In the validation procedure, the serum concentrations of VPA from the population PK-Valid group were predicted by base and final models respectively. To assess the accuracy and precision of the predictions, mean prediction error （MPE）, mean squared prediction error （MSPE）, root mean squared prediction error （RMSPE）, weight-residues （WRES） and its 95 % confidence intervals （95 % CI） were all calculated, then compared between the two models. For population PD group, all of the ! 15 patients were VPA monotherapy. Efficacy of epilepsy treatment was divided into 5 grades according to the percentage of seizure frequency decreased （ PSFD% ）. The value of PSFD% 100%, 75% - 100%, 50% - 75%, 25% - 50%, or less than 25 % are corresponding to grade 1 to 5. For population PD group, the quantitative relationship between the VPA serum concentrations and the probability for its efficacy score was characterized by logistic regression.

关 键 词：中国 癫痫儿童 丙戊酸钠 群体模型 药动学模型 药效学模型 

分 类 号：R971.6[医药卫生—药品]