Population Pharmacokinetic Parameters of Valproic Acid; Conventional and Slow Release Formulation.

Abstract

A population pharmacokinetic analysis of valproic acid in conventional and slow release formulations was carried out. Three hundred and forty-four points in two hundred and fifteen patients were analyzed. The pharmacokinetic model, which took into account the age of the patients and the absorption lag time of the slow release formula tions, and a pharmacostatistical model with individual and residual variability were evaluated. The influence of the age of the patients and the absorption lag time on the valproic acid pharmacokinetics was significant based on the results of the statistical test. The ka of slow release formulations was 0.230 (1/h), the ka of conventional formulations was 8.14 (1/h), the Vd of the conventional and slow release formulations was 0.212 (L/kg) and the ke of the conventional and slow release formulations was 0.0495 (1/h) in adults (≥12 years) and the lag time of the slow release formulations was 1.25 (h). The ka changed with the patient's age. The ka was different for conventional and slow release formulations. Though conventional formulations did not have a lag time, the slow release formulations had a lag time. The patient age and the lag time are thought to be included in the population pharmacokinetic model using a slow release formulation. The findings suggest that the values obtained for these population pharmacokinetic parameters will be useful in optimizing valproic acid therapy for individual patients.