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Influence of co-medication on the metabolism of valproate

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Abstract

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. Δ 2-valproate, 3-OH-valproate and 3-oxo-valproate, and an increase of glucuronidation (approximately 30%) andδ-dehydrogenation (approximately 20%). Stiripentol inhibits the formation clearance ofΔ 4-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.

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  1. First Neurological Clinic, University of Messina, 98013, Contessa-Messina, Italy

    Francesco Pisani

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Pisani, F. Influence of co-medication on the metabolism of valproate. Pharmaceutisch Weekblad Scientific Edition 14, 108–113 (1992). https://doi.org/10.1007/BF01962698

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