title: Pharmacokinetics and anticonvulsant activity of three monoesteric prodrugs of valproic acid.
abstract: The pharmacokinetics of valproic acid (VPA) were compared in dogs with those of the prodrugs ethyl valproate (E-VPA), trichloroethyl valproate (T-VPA), and valproyl valproate (V-VPA). Valproic acid, E-VPA, T-VPA, and V-VPA were administered intravenously and orally to six dogs at equimolar doses. The three VPA prodrugs were rapidly converted to VPA. The biotransformation was complete in the case of E-VPA and T-VPA but was only partial in the case of V-VPA. Because of the rapid conversion to the parent drug, after administration of the prodrugs, VPA plasma levels did not yield a sustained-release profile. Further, the anticonvulsant activity of prodrugs was compared in mice to that of VPA and valpromide (VPD). The anticonvulsant activity of E-VPA, T-VPA, and V-VPA was less than that of VPA.
authors.affiliation: Department of Pharmacy, School of Pharmacy, Hebrew University of Jerusalem, Israel.
authors.forename: K
authors.initials: K
authors.lastname: Badir
authors.forename: A
authors.initials: A
authors.lastname: Haj-Yehia
authors.forename: T B
authors.initials: TB
authors.lastname: Vree
authors.forename: E
authors.initials: E
authors.lastname: van der Kleijn
authors.forename: M
authors.initials: M
authors.lastname: Bialer
mesh_terms: D000818:Animals; D004285:Dogs; D005260:Female; D008297:Male; D011355:Prodrugs / Q000493:pharmacokinetics* / Q000494:pharmacology; D014635:Valproic Acid / Q000031:analogs & derivatives / Q000493:pharmacokinetics* / Q000494:pharmacology
chemical_list: D011355:Prodrugs; D014635:Valproic Acid