Modification of phenytoin clearance by valproic acid in normal subjects.

GM Frigo, S. Lecchini, G. Gatti, E. Perucca, A. Crema

Research output: Contribution to journalArticlepeer-review


1 The effect of valproic acid on the distribution and elimination kinetics of intravenously administered phenytoin has been investigated in eight normal volunteers. 2 In each of the subjects studied the volume of distribution of phenytoin increased significantly during treatment with sodium valproate (1200 mg daily for 7 days). 3 Phenytoin clearance was markedly increased in presence of valproic acid as compared to control values (0.52 +/‐ 0.17 v 0.38 +/‐ 0.11 ml min‐1 kg‐1 respectively, P less than 0.02). 4 It is suggested that the increase of the volume of distribution and of the serum clearance are secondary to displacement of phenytoin from plasma protein binding sites by valproic acid. 1979 The British Pharmacological Society

Original languageEnglish
Pages (from-to)553-556
Number of pages4
JournalBritish Journal of Clinical Pharmacology
Issue number6
Publication statusPublished - 1979

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology
  • Pharmacology, Toxicology and Pharmaceutics(all)


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