Valproic Acid: Reversibly Acting Drug?

Valproic acid [dipropylacetic acid (DPA)] was evaluated in an alumina-gel monkey model (N= 12) by constant-rate intravenous infusion. The data indicated: (a) a statistically significant decrease in seizure frequency the first 2 days of drug Step I (45–55 μg/ml) and drug Step II (90–110 μg/ml) which was temporary, lasting 2 days only; (b) a later, more permanent decrease in seizure frequency which was not apparent until drug Step III (130–170 μg/ml); and a delayed return of the seizure frequency to predrug levels for 2 weeks after drug administration was discontinued, with no DPA detectable in plasma after the initial postdrug day. Whether DPA will behave as a reversibly acting drug was discussed.