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Pharmaceutisch Weekblad

, Volume 14, Issue 3, pp 122–125 | Cite as

Metabolism of valproate to hepatotoxic intermediates

  • Thomas A. Baillie
Recent Developments on Valproate and its Metabolites

Abstract

A number of lines of evidence indicate that metabolites of valproate rather than the parent drug, mediate the microvesicular steatosis which characterizes valproate-associated liver injury. In this article, two mechanisms are discussed whereby valproate may cause hepatic steatosis through interference with the process of fatty acidβ-oxidation. In the first, valproate itself enters the mitochondrion where it competes for the enzymes and/or co-factors involved in theβ-oxidation of endogeneous substrates, while in the second, valproate is metabolized via the hepatotoxic terminal olefin, Δ4-valproate, to a variety of chemically reactive intermediates which inhibit key enzymes in theβ-oxidation cycle.

Keywords

Biotransformation Fatty acid oxidation Liver diseases 2-n-Propyl-4-pentenoic acid Steatosis Valproic acid 

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Copyright information

© Royal Dutch Association for Advancement of Pharmacy 1992

Authors and Affiliations

  • Thomas A. Baillie
    • 1
  1. 1.Department of Medicinal Chemistry, School of Pharmacy, BG-20University of WashingtonSeattleUSA

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