Valproic acid disposition in epileptic patients during combined antiepileptic maintenance therapy

A previously developed mass spectrometric method was used to measure, in the presence of the unlabeled drug, the fate of pulse dose of tetradeuterated valproic acid given to epileptic patients. By this means the disposition of valproic acid (VPA) was studied in several epileptic patients on maintenance therapy with VPA and at least one other anti-epileptic drug. For 6 patients with 6 different anti-epileptic drug combinations, the mean VPA half-life was only 6.2 h, as compared to about 15 h after a single dose. The mean plasma clearance in those patients was 16.4 ml/min. The volume of distribution was 0.14 l/kg, which did not differ from values found in single dose studies. The clinical relevance of these findings is pointed out.