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Effects of sodium valproate on haem biosynthesis in man: implications for seizure management in the porphyric patient
Author(s) -
McGUIRE G. M.,
MACPHEE G. J. A.,
THOMPSON G. G.,
MOORE M. R.,
BRODIE M. J.
Publication year - 1988
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/j.1365-2362.1988.tb01161.x
Subject(s) - dehydratase , porphobilinogen , porphobilinogen deaminase , medicine , uroporphyrinogen iii decarboxylase , endocrinology , chemistry , urinary system , excretion , porphyria , porphobilinogen synthase , heme , enzyme , acute intermittent porphyria , biochemistry
. 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 ( P <0·001). This was accompanied by increased urinary excretion of 5‐aminolaevulinic acid (ALA; P <0·02) and total porphyrins ( P <0·01). Mean (± SD) total VPA concentrations on day 3 (89 ± 16 mg l ‐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 ( P <0·001), and daily urinary excretion of porphobilinogen ( P <0·01) and total porphyrins ( P <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.