Pharmacokinetics of valproic acid in children: I. Multiple antiepileptic drug therapy.

We studied the pharmacokinetics of valproic acid (VPA) in 37 children who were taking other antiepileptic drugs. Thirteen children were studied both after initial and while on maintenance valproic acid therapy. Significant differences occurred between initial and maintenance therapy in the mean apparent volume of distribution and in apparent VPA clearance, whereas VPA half-life remained relatively constant. Analysis of data in the 13 children studied on two occasions demonstrated wide intrapatient variability of VPA pharmacokinetics. Children taking VPA together with other antiepileptic medications generally require higher doses of VPA given more frequently.