首页|Population pharmacokinetics modeling of levetiracetam in Chinese children with epilepsy
Population pharmacokinetics modeling of levetiracetam in Chinese children with epilepsy
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NETL
NSTL
万方数据
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)=0.988 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=1.04×(WEIG/25)0.563 (L/h).For the basic model,the MPE,MSPE,RMSPE,WRES,and the 95％CI 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％ CI 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 first-order 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.
levetiracetamepilepsypopulation pharmacokineticspediatricChinese children
NETL
NSTL
万方数据
