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. 1979 Dec;8(6):553–556. doi: 10.1111/j.1365-2125.1979.tb01043.x

Modification of phenytoin clearance by valproic acid in normal subjects.

G M Frigo, S Lecchini, G Gatti, E Perucca, A Crema
PMCID: PMC1429910  PMID: 391257

Abstract

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.

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Selected References

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