TY - JOUR T1 - Studies on the biotransformation in the perfused rat liver of 2-n-propyl-4-pentenoic acid, a metabolite of the antiepileptic drug valproic acid. Evidence for the formation of chemically reactive intermediates. JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 81 LP - 96 VL - 13 IS - 1 AU - A W Rettenmeier AU - K S Prickett AU - W P Gordon AU - S M Bjorge AU - S L Chang AU - R H Levy AU - T A Baillie Y1 - 1985/01/01 UR - http://dmd.aspetjournals.org/content/13/1/81.abstract N2 - The metabolism of 2-n-propyl-4-pentenoic acid (delta 4-VPA), a putative toxic biotransformation product of valproic acid (VPA), was examined in the isolated perfused rat liver. Metabolites excreted into perfusion medium and bile were characterized by GLC and GC/MS techniques and their identities were verified by synthesis. A total of eight metabolites was detected, the structures of which could be best accounted for by initial oxidation reactions catalyzed by either cytochrome P-450 or the fatty acid beta-oxidation complex. Evidence was obtained which indicates that metabolism of delta 4-VPA by each of these enzyme systems can lead to the generation of chemically reactive intermediates which may contribute to the hepatotoxic properties of VPA. ER -