Modification of phenytoin clearance by valproic acid in normal subjects.
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.
D000328:Adult; D005260:Female; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D007700:Kinetics; D008297:Male; D010672:Phenytoin / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D013997:Time Factors; D014635:Valproic Acid / Q000494:pharmacology*
D014635:Valproic Acid; D010672:Phenytoin