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

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Abstract
The pharmacoknetics of volproic acid were investigated in 6 healthy volunteers. After a single i.v. dose of 1000 mg valproic acid, the pharmocokinetic parameters were determined according to the open 2-compartment model. Bioavailability of valproic acid was performed by comparing the areas under curves (AUC) after i.v. and an equal single oral dose. The half-life of the initial phase was t1/2.alpha. = 0.64 .+-. 0.32 h, and the elimination half-life was calculated as t1/2.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 voluem 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. In comparison to single dosing, the elimination half-life increased in average for 4 h after multiple dosing (P .ltoreq. 0.05). There was only a poor correlation between serum concentrations and concentration of valproic acid in saliva (r = 0.42).

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