Valproic Acid: Reversibly Acting Drug?

Abstract

Valproic acid [dipropylacetic acid (DPA)] was evaluated in an alumina-gel monkey [rhesus] model (N = 12) by constant-rate i.v. infusion. The data indicated a statistically significant decrease in seizure frequency the first 2 days of drug Step I (45-55 .mu.g/ml) and drug Step II (90-110 .mu.g/ml) which was temporary, lasting only 2 days, and a later, more permanent decrease in seizure frequency which was not apparent until drug Step III (130-170 .mu.g/ml). A delayed return of the seizure frequency to predrug levels for 2 wk was also observed 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.