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OBJECTIVE:To realize personalized medicine on the basis of population pharmacokinetics (PopPK) of valproic acid (VPA) in children with epilepsy.METHODS:The clinical data and VPA plasma concentrations of children with epilepsy in Beijing Tiantan Hospital (2011.5-2013.5) were collected, nonlinear mixed effect modeling method was used to set up PopPK of VPA.A one compartment pharmacokinetic model with first-order absorption and elimination was used to describe the concentration-time data.The first order conditional estimation with η-ε interaction (FOCE-I) was used throughout the model building procedure.Absorption rate constant (ka) was fixed as 2.38 h-1.On the basis of basic model, the influence of physiological factors and drug combinations on relative clearance (Cl/F) and apparent volume of distribution (V) were investigated using NONMEM program.Based on the final PopPK and Bayesian estimation, the personalized medicine were optimized.RESULTS: 113 pediatric inpatients and 205 plasma VPA concentrations were collected retrospectively.The final population parameters were as follow: Cl/F =0.13 + 0.02×Age + 0.04×LTG L·h-1, V/F =7.40 + 23.4×Tablet L, ka =2.38 h-1.Where LTG was 1 when co-medicated with lamotrigine (LTG), otherwise LTG was 0.Where Tablet was 1 when patient take VPA tablets, otherwise Tablet was 0.A reliable results were got when using PopPK model to predict the drug concentrations.CONCLUSION The final PopPK model was reliable to estimate the individual Cl/F and V for pediatric patients receiving VPA.