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The effects of valproic acid on liver function.

F A de Wolff, A C Peters, G M van Kempen

    Archives of Toxicology. Supplement. = Archiv Fur Toxikologie. Supplement
    |January 1, 1983
    PubMed
    Summary

    Valproic acid (VPA) did not increase liver enzyme activity in epileptic children but enhanced D-glucaric acid (GLA) excretion. This VPA effect on GLA was also observed in guinea pigs, alongside liver cell changes.

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    Area of Science:

    • Pharmacology
    • Biochemistry
    • Pediatric Neurology

    Background:

    • Valproic acid (VPA) is a widely used antiepileptic drug.
    • Concerns exist regarding VPA's potential enzyme-inducing effects and hepatotoxicity.
    • Gamma-glutamyltranspeptidase (GGT) is a marker for liver enzyme induction, while D-glucaric acid (GLA) excretion may reflect altered drug metabolism.

    Purpose of the Study:

    • To investigate the enzyme-inducing potential of VPA in children with epilepsy.
    • To assess the effect of VPA on serum GGT activity and urinary GLA excretion.
    • To explore the VPA-induced GLA excretion phenomenon in an animal model.

    Main Methods:

    • Serum GGT activity and urinary GLA excretion were measured in 32 epileptic children on VPA monotherapy.
    • VPA was administered to guinea pigs to evaluate its effect on GLA excretion and liver histology.
    • Statistical analysis was performed to determine the significance of observed changes.

    Main Results:

    • VPA monotherapy in children did not significantly alter serum GGT activity.
    • VPA selectively enhanced urinary GLA excretion in epileptic children.
    • In guinea pigs, VPA administration increased GLA excretion and caused cytoplasmic vacuolization in hepatic cells.
    • A potential link between VPA-induced GLA excretion and hepatotoxicity was suggested but not confirmed.

    Conclusions:

    • VPA does not appear to induce GGT activity in children at the studied dosage.
    • VPA selectively stimulates GLA excretion in both epileptic children and guinea pigs.
    • Further research is needed to elucidate the relationship between VPA-induced GLA excretion and potential hepatotoxicity.

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