Effects of sodium valproate on haem biosynthesis in man: implications for seizure management in the porphyric patient

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Abstract
The short‐term effects of sodium valproate (VPA) on haem biosynthesis were assessed in a placebo‐controlled crossover trial in eight healthy male subjects who ingested VPA 500 mg t.i.d. and matched placebo for 5 days. All showed augmented activity of leucocyte 5‐aminolaevulinate synthase (ALA‐S) activity, the rate‐limiting enzyme of the haem biosynthetic pathway, following 3 and 5 days of VPA treatment (PPP‐1) and day 5 (91 ± 22 mg l‐1) were within the target range for the drug. The long‐term effects of VPA administration were examined in epileptic patients on established monotherapy. Leucocyte ALA‐S activity (PPP<0·01) were all higher than in age‐matched controls. No significant differences in erythrocyte ALA‐dehydratase, porphobilinogen deaminase and uroporphyrinogen decarboxylase activities were found between the groups. These data suggest that VPA is porphyrinogenic in man and cannot be recommended as safe for seizure management in the porphyric patient.