Effect of sustained release on the pharmacokinetics of valproic acid in the dog

The effect of sustained release on the pharmacokinetics of valproic acid was examined by comparing 4 test sustained-release formulations to a standard tablet and an i.v. preparation of the drug. Drug level monitoring in the plasma was performed by a GLC assay. Results indicate that 3 sustained-release formulations exhibited a more prolonged and uniform absorption rate, yielded more sustained plasma levels after injection, and showed an overall bioavailability of 0.81, 0.78 and 0.40, respectively, relative to an equivalent dose of a conventional tablet. The absorption profile of the various oral formulations were pharmacokinetically analyzed by using the Loo-Riegelman procedure.