European Journal of Clinical Investigation

Volume 18, Issue 1 pp. 29-32

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

G. M. McGUIRE,

G. M. McGUIRE

University Department of Medicine, Gardiner Institute, Western Infirmary, Glasgow, U.K.

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G. J. A. MACPHEE,

G. J. A. MACPHEE

University Department of Medicine, Gardiner Institute, Western Infirmary, Glasgow, U.K.

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G. G. THOMPSON,

G. G. THOMPSON

University Department of Medicine, Gardiner Institute, Western Infirmary, Glasgow, U.K.

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M. R. MOORE,

M. R. MOORE

University Department of Medicine, Gardiner Institute, Western Infirmary, Glasgow, U.K.

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M. J. BRODIE,

Corresponding Author

M. J. BRODIE

University Department of Medicine, Gardiner Institute, Western Infirmary, Glasgow, U.K.

² Clinical Pharmacology Unit, University Department of Medicine, Western Infirmary, Glasgow G11 6NT, U.K.Search for more papers by this author

G. M. McGUIRE,

G. M. McGUIRE

University Department of Medicine, Gardiner Institute, Western Infirmary, Glasgow, U.K.

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G. J. A. MACPHEE,

G. J. A. MACPHEE

University Department of Medicine, Gardiner Institute, Western Infirmary, Glasgow, U.K.

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G. G. THOMPSON,

G. G. THOMPSON

University Department of Medicine, Gardiner Institute, Western Infirmary, Glasgow, U.K.

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M. R. MOORE,

M. R. MOORE

University Department of Medicine, Gardiner Institute, Western Infirmary, Glasgow, U.K.

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M. J. BRODIE,

Corresponding Author

M. J. BRODIE

University Department of Medicine, Gardiner Institute, Western Infirmary, Glasgow, U.K.

² Clinical Pharmacology Unit, University Department of Medicine, Western Infirmary, Glasgow G11 6NT, U.K.Search for more papers by this author

First published: February 1988

https://doi.org/10.1111/j.1365-2362.1988.tb01161.x

Citations: 12

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Abstract

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 (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.

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Volume18, Issue1

February 1988

Pages 29-32

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

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

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