Management of Neurologic Exacerbations of Hepatic Porphyria

Sergay, Stephen M.

doi:10.1016/s0025-7125(16)31710-2

Cited by 15 publications

(3 citation statements)

References 29 publications

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“…Conclusions regarding the effects of VPA on haem biosynthesis have previously been based on studies in rodent model systems or on anecdotal case reports [14][15][16][17][18]. Conclusions regarding the effects of VPA on haem biosynthesis have previously been based on studies in rodent model systems or on anecdotal case reports [14][15][16][17][18].…”

Section: Discussionmentioning

confidence: 99%

“…Sodium valproate is a branched-chain fatty acid established as a first-line agent in the management of epilepsy [ 131. Conclusions regarding the effects of VPA on haem biosynthesis have previously been based on studies in rodent model systems or on anecdotal case reports [14][15][16][17][18]. In this paper the results of a controlled experiment in man are presented.…”

Section: Discussionmentioning

confidence: 99%

“…One such is sodium valproate (VPA) (Epilimm), a first-line anti-epileptic drug effective in the management of generalized tonic-clonic, absence, partial and myoclonic seizures [ 131. Whereas many workers argue from data gleaned from case repots, in-vitro systems and animal systems against the use of VPA for seizure management in porphyria [9,14-171, others have suggested otherwise [18,19]. This study was designed to examine the effects of acute and chronic VPA administration on haem biosynthesis in man.…”

Section: Introductionmentioning

confidence: 99%

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

McGUIRE

Macphee

Thompson

et al. 1988

Eur J Clin Investigation

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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 less than 0.001). This was accompanied by increased urinary excretion of 5-aminolaevulinic acid (ALA; P less than 0.02) and total porphyrins (P less than 0.01). Mean (+/- SD) total VPA concentrations on day 3 (89 +/- 16 mg 1-1) and day 5 (91 +/- 22 mg 1-1) 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 less than 0.001), and daily urinary excretion of porphobilinogen (P less than 0.01) and total porphyrins (P less than 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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