Population pharmacokinetics of intravenous valproic acid in Korean patients

Abstract

Objective: To determine population‐based pharmacokinetic parameters for intravenous valproic acid, and the factors influencing these parameters, in Korean adults. Methods: Valproic acid concentrations were obtained using a peak and trough sampling scheme for 102 Korean epileptic patients who were not taking concurrent antiepileptic medication. Three hundred and fifty‐four serum concentrations were analysed according to a one‐compartment model with a mixed effect modelling method (NONMEM Ver 5·0). The influence of body‐weight (kg), height, daily valproic acid dose (mg/day), body mass index (kg/m²), sex, and age on volume of distribution (Vd) and clearance (CL) was assessed in the course of analysis. Results: Vd and CL of valproic acid increased with body‐weight. No significant influence of the other screened covariates was observed. The final regression model was: Interindividual variabilities (coefficient of variation) for CL and Vd were 32 and 18%, respectively. Residual error including intraindividual variability was 26·7%. Conclusion: The current results may be used as a basic reference to optimize drug therapy with intravenous valproic acid. Further research on the paediatric population is necessary to confirm the non‐linearity of the relation between body‐weight and Vd.