Modification of phenytoin clearance by valproic acid in normal subjects.
- 1 December 1979
- journal article
- clinical trial
- Published by Wiley in British Journal of Clinical Pharmacology
- Vol. 8 (6), 553-556
- https://doi.org/10.1111/j.1365-2125.1979.tb01043.x
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.Keywords
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