Pharmacokinetics and anticonvulsant activity of three monoesteric prodrugs of valproic acid.
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.
Badir
K
K
Department of Pharmacy, School of Pharmacy, Hebrew University of Jerusalem, Israel.
Haj-Yehia
A
A
Vree
T B
TB
van der Kleijn
E
E
Bialer
M
M
D000818:Animals; D004285:Dogs; D005260:Female; D008297:Male; D011355:Prodrugs / Q000493:pharmacokinetics* / Q000494:pharmacology; D014635:Valproic Acid / Q000031:analogs & derivatives / Q000493:pharmacokinetics* / Q000494:pharmacology
D011355:Prodrugs; D014635:Valproic Acid