Pharmaceutisch Weekblad

, Volume 14, Issue 3, pp 108–113 | Cite as

Influence of co-medication on the metabolism of valproate

  • Francesco Pisani
Recent Developments on Valproate and its Metabolites


Valproate is extensively metabolized in the liver and at least six main pathways which produce about 50 metabolites have been identified in man. The enzyme-inducing antiepileptic drugs phenobarbital, primidone, phenytoin and carbamazepine increase total valproate clearance by 30–85%, whereas cimetidine and the new anticonvulsant compound striripentol display a small inhibitory effect (10–20%). Both carbamazepine and phenytoin induce a two-fold increase in the formation of Δ4-valproate and stimulateω-oxidation andω-1-oxidation. Acetylsalicylic acid causes a fall of 60–70% in the content in the urine of the metabolites of theβ-oxidative pathway,i.e.Δ2-valproate, 3-OH-valproate and 3-oxo-valproate, and an increase of glucuronidation (approximately 30%) andδ-dehydrogenation (approximately 20%). Stiripentol inhibits the formation clearance ofΔ4-valproate by 30%. In the light of the possible therapeutic and toxic effects of some valproate metabolites, drug interactions with valproate at metabolic level may have important clinical implications.


Acetylsalicylic acid [Anticonvulsants Biotransformation Cimetidine Drug interactions Liver diseases Metabolites Pharmacokinetics Valproic acid 


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Copyright information

© Royal Dutch Association for Advancement of Pharmacy 1992

Authors and Affiliations

  • Francesco Pisani
    • 1
  1. 1.First Neurological ClinicUniversity of MessinaContessa-MessinaItaly

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