Journal Article

Population pharmacokinetics modeling of evetiracetam in Chinese children with epilepsy

Ying-hui WANG Li WANG Wei LU De-wei SHANG Min-ji WEI Ye WU

2012

Overview

Aim： To establish a population pharmacokinetics （PPK） model of levetiracetam in Chinese children with epilepsy. Methods： A total of 418 samples from 361 epileptic children in Peking University First Hospital were analyzed. These patients were divided into two groups： the PPK model group （n=311） and the PPK validation group （n=50）. Levetiracetam concentrations were determined by HPLC. The PPK model of levetiracetam was established using NONMEM, according to a one-compartment model with firstorder absorption and elimination. To validate the model, the mean prediction error （MPE）, mean squared prediction error （MSPE）, root mean-squared prediction error （RMSPE）, weight residues （WRES）, and the 95% confidence intervals （95% CI） were calculated. Results： A regression equation of the basic model of levetiracetam was obtained, with clearance （CL/F）=O.988 L/h, volume of distribution （V/F）=12.3 L, and Ka=1.95 h-1. The final model was as follows： Ka=1.56 h-1, V/F=12.1 （L）, CL/F=1.04x（WEIG/25）63 （L/h）. For the basic model, the MPE, MSPE, RMSPE, WRES, and the 95%Cl were 9.834 （-0.587-197.720）, 50.919 （0.012-1286.429）, 1.680 （0.021-34.184）, and 0.0621 （-1.100-1.980）. For the final model, the MPE, MSPE, RMSPE, WRES, and the 95% Cl were 0.199 （-0.369-0.563）, 0.002082 （0.00001-0.01054）, 0.0293 （0.001-0.110）, and 0.153 （-0.030-1.950）. Conclusion： A one-compartment model with firstrder absorption adequately described the levetiracetam concentrations. Body weight was identified as a significant covariate for levetiracetam clearance in this study. This model will be valuable to facilitate individualized dosage regimens.

• Subject: 中国 / 儿童 / 动力学建模 / 北京大学第一医院 / 癫痫 / 群体 / 预测误差 / 高效液相色谱法