The pharmacokinetics of valproic acid after oral and parenteral administration in healthy volunteers.

The pharmacokinetics of valproic acid were investigated in six healthy volunteers. After a single intravenous dose of 1,000 mg valproic acid, the pharmacokinetic parameters were determined according to the open two-compartment model. Bioavailability of valproic acid was performed comparing the areas under curves (AUC) after i.v and an equal single oral dose. The half-life of the initial phase was t 1/2 alpha = 0.64 +/- 0.32 h, and the elimination half-life was calculated as t 1/2 beta = 11.55 +/- 2.33 h. The distribution volume of the central compartment was Vc = 9.9 +/- 0.78 L, the apparent volume of distribution was Vd beta = 18.2 +/- 6.2 L, and the distribution volume at steady state was Vss = 12.6 +/- 1.2 L. The value for the average total clearance was Cltot = 51.1 +/- 11.9 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 less than or equal to 0.05). There was only a poor correlation between serum concentrations and concentration of valproic acid in saliva (r = 0.42).