Assays - Valproic acid

The Pharmacokinetics of Valproic Acid After Oral and Parenteral Administration in Healthy Volunteers

Author: V. Nitsche, H.J. Mascher
Publisher: Epilepsia 23 (1982), 153-162

The pharmacokinetics of valproic acid were investigated in six healthy volunteers. After a single intravenous dose of 1000 mg valproic acid, the pharmacokinetic parameters were determined according to the open two-compartment model. Bioavailability of valproic acid was performed comparing the areas und curves (AUC) after i.v. and an equal single oral dose. The half-life of the initial phase was 0.64 h, and the elimination half-life was calculated as 11.55 h. The distribution volume of the central compartment was 9.9 L, the apparent volume of distribution was 18.2 L, and the distribution volume at steady state was 12.6 L. The value for the average total clearance was 51.1 ml/min. The study showed that in comparison to single dosing, the elimination half-life increased in average for four hours after multiple dosing (p ≤ 0.05). There was only a poor correlation between the serum concentrations and concentration of valproic acid in saliva (r = 0.42).