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  • Title: Pharmacokinetic analysis and anticonvulsant activity of two polyesteric prodrugs of valproic acid.
    Author: Hadad S, Vree TB, van der Kleijn E, Bialer M.
    Journal: Biopharm Drug Dispos; 1993 Jan; 14(1):51-9. PubMed ID: 8427944.
    Abstract:
    The pharmacokinetics of the following two polyesteric prodrugs of valproic acid (VPA) have been investigated: 1,4-butanediol divalproate (BDV) and glyceryl trivalproate (GTV). In addition, the anticonvulsant activity of these compounds has been evaluated and compared to that of VPA and valpromide (VPD). Valproic acid, and its two esteric derivatives were administered intravenously to six dogs at an equivalent dose (400 mg VPA) and their pharmacokinetics investigated. In the case of BDV, the biotransformation to VPA was complete, but in the case of GTV, it was only partial. Of the two investigated esteric prodrugs of VPA, only BDV demonstrated anticonvulsant activity and showed less neurotoxicity than VPA and VPD, and therefore had a better protective index. The anticonvulsant activity is explained on pharmacokinetic and pharmacodynamic grounds due to its complete conversion to VPA and the possible synergism in anticonvulsant activity between VPA and 1,4-butanediol.
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