Population pharmacokinetics of valproate in Chinese children with epilepsy

Aim:The aim of the present study is to establish a population pharmacokinetic(PPK) model of valproate (VPA) in Chinese epileptic children to promote thereasonable use of anti-epileptic drugs.Methods:Sparse data of VPA serumconcentrations from 417 epileptic children were collected.These patients weredivided into 2 groups:the PPK model group (n=317) and the PPK valid group(n=100).The PPK parameter values of VPA were calculated by NONMEM soft-ware using the data of the PPK model group.A basic model and a final modelwere set up.To validate the 2 models,the concentrations of PPK valid groupwere predicted by each model,respectively.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 also calculated.Then,the values between the 2 models were compared.Results:The PPK of VPA was determined by a 1-compartment model with afirst-order absorption process.The basic model was:Ka=3.09 (h-1),V/F=20.4(L),CL/F=0.296 (L/h).The final model was:Ka=0.251+2.24·(1-HS)(h-1),V/F=2.88+0.157·WT (L),CL/F=0.1060.98·CO+0.0157·AGE (L/h).For thebasic model,the MPE,MSPE,RMSPE,WRES,and the 95% CI were-23.53(-30.36,-16.70),3728.96 (2872.72,4585.20),39.62 (34.34,44.90),and-0.06 (-0.14,0.02),respectively.For the final model,the MPE,MSPE,RMSPE,WRES,and the95% CI were-1.16 (-4.85,2.53),1002.83 (1050.64,1143.61),23.04 (21.12,24.96),and0.08 (-0.04,0.20),respectively.The final model was more optimal than the basicmodel.Conclusion:The PPK model of VPA in Chinese epileptic children wassuccessfully established.It will be valuable to facilitate individualized dosageregimens.