PHARMACOKINETIC ANALYSIS OF VALDICE - A DIETHYLCARBONATE PRODRUG OF VALPROIC ACID

The pharmacokinetics of valdice, a new diethylcarbonate prodrug of valproic acid (VPA), was investigated in humans and dogs. In both species valdice was biotransformed to VPA and no valdice was detected in the plasma following its oral administration. The relative bioavailability of VPA following oral administration of valdice was 79% in dogs and 94-99% in humans, in comparison to commercially available tablets of VPA. In humans valdice showed a longer tmax value than two commercial enteric coated products of VPA, Depakine 500 and Depakote. Nevertheless, the MRT values of the three investigated VPA products were similar. The current study showed that in humans valdice exhibited a controlled rate of delivery of VPA although it did not show an in vivo sustained release performance like a once daily sustained release (SR) product of VPA.