title: Markedly increased omega-oxidation of valproate in fulminant hepatic failure.
abstract: Using gas chromatography-mass spectrometry, we showed that the urinary metabolite profile of valproate (VPA) in a subject receiving VPA and phenobarbital (PB) who died of fulminant hepatic failure was quite different from those of reported patients with Reye's syndrome or fatal hepatic failure. Only 2-n-propylglutarate, the end product of omega-oxidation of VPA, was excreted in markedly increased amounts, while other VPA metabolites were undetectable. Although the primary cause of fulminant hepatitis and the mechanism of enhanced VPA metabolism by the hepatic P-450 system in this patient are not clear, our findings suggest that P-450-mediated reactions become the predominant metabolic pathway of VPA in a stage of fulminant hepatic failure.
authors.affiliation: Division of Human Genetics, Kanazawa Medical University, Ishikawa, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kuhara
authors.forename: Y
authors.initials: Y
authors.lastname: Inoue
authors.forename: M
authors.initials: M
authors.lastname: Matsumoto
authors.forename: T
authors.initials: T
authors.lastname: Shinka
authors.forename: I
authors.initials: I
authors.lastname: Matsumoto
authors.forename: N
authors.initials: N
authors.lastname: Kawahara
authors.forename: N
authors.initials: N
authors.lastname: Sakura
mesh_terms: D056486:Chemical and Drug Induced Liver Injury; D002675:Child, Preschool; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D008107:Liver Diseases / Q000652:urine; D008297:Male; D010084:Oxidation-Reduction; D014635:Valproic Acid / Q000009:adverse effects* / Q000652:urine
chemical_list: D014635:Valproic Acid