Pharmacokinetics of valproic acid obtained after administration of three oral formulations to humans.

The pharmacokinetics and bioavailability of valproic acid (VPA) were compared in six healthy volunteers after oral administration of the drug as follows: 1 g in standard tablet form, 1 g in enteric-coated tablet form, and 0.8 g in gelatin-capsule form. Following the administration of standard tablets, VPA concentrations reached a peak mean +/- SD of 105.4 +/- 9.0 micrograms/ml at 1 h and declined monoexponentially, with a terminal half-life of 14.9 +/- 2.4 h. Following the administration of the capsule, the serum concentration reached a peak of 82.1 +/- 14.8 micrograms/ml at 4 h. Following the administration of an enteric-coated tablet, there was an average time lag of 2 h with a delayed peak serum concentration of 93.5 +/- 13.1 micrograms/ml at 6 h. An identical terminal half-life of VPA was obtained for the three oral formulations. The bioavailability of the three VPA formulations was not significantly different, and it may be concluded that these formulations are bioequivalent.