STUDIES ON THE BIOTRANSFORMATION IN THE PERFUSED RAT-LIVER OF 2-NORMAL-PROPYL-4-PENTENOIC ACID, A METABOLITE OF THE ANTIEPILEPTIC DRUG VALPROIC ACID - EVIDENCE FOR THE FORMATION OF CHEMICALLY REACTIVE INTERMEDIATES

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  • 1 January 1985
    • journal article
    • research article
    • Vol. 13  (1) , 81-96
Abstract
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 [gas chromatography/mass spectrometry] techniques and their identities were verified by synthesis. Eight metabolites were 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. Metabolism of .DELTA.4-VPA by each of these enzyme systems can evidently lead to the generation of chemically reactive intermediates which may contribute to the hepatotoxic properties of VPA.