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PMID: 391257 Published · ppublish English Clinical Trial Journal Article Randomized Controlled Trial

Modification of phenytoin clearance by valproic acid in normal subjects.

British journal of clinical pharmacology ·Vol. 8 ·No. 6 ·1979-12-00 ·Pages 553-6

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

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.

MeSH Terms

Adult Female Half-Life Humans Injections, Intravenous Kinetics Male Phenytoin/administration & dosage,blood,metabolism Time Factors Valproic Acid/pharmacology

Chemicals

Valproic Acid Phenytoin

Authors & Affiliations

5 authors, click to expand affiliations / ORCID

Frigo G M

Lecchini S

Gatti G

Perucca E

Crema A

References (15)

15 references, click to expand

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Valproic acid in epilepsy: clinical and pharmacological effects.
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Determination of the anticonvulsant drug--dipropyl acetate (Epilim) in human plasma by gas chromatography.
Ann Clin Biochem. 1977 Jul;14(4):240-2 PMID: 332044
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Changes in drug metabolism with increasing age: 2. phenytoin clearance and protein binding.
Br J Clin Pharmacol. 1975 Feb;2(1):73-9 PMID: 1234490
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N Engl J Med. 1976 Mar 4;294(10):526-31 PMID: 765821
Commentary: a physiological approach to hepatic drug clearance.
Clin Pharmacol Ther. 1975 Oct;18(4):377-90 PMID: 1164821
Kinetics of diphenylhydantoin in uraemic patients: consequences of decreased plasma protein binding.
Eur J Clin Pharmacol. 1974;7(1):31-7 PMID: 4852619
Letter: Effect of plasma protein binding on elimination of warfarin.
J Pharm Sci. 1974 May;63(5):805-6 PMID: 4830012
Micromethod for the determination of diphenylhydantoin in plasma and cerebrospinal fluid--a comparison between a gas chromatographic and a spectrophotometric method.
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Serum protein binding as a determinant of warfarin body clearance and anticoagulant effect.
Clin Pharmacol Ther. 1976 May;19(5 Pt 1):552-8 PMID: 1277711
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Article Info

Journal

British journal of clinical pharmacology

Abbr.

Br J Clin Pharmacol

ISSN

0306-5251

DOI

10.1111/j.1365-2125.1979.tb01043.x

Published

1979-12-00

Pages

553-6

Language

English

Region

England

NLM ID

7503323

PMCID

PMC1429910

Subset

External Links

PubMed source DOI: 10.1111/j.1365-2125.1979.tb01043.x PMC Full Text View journal details

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Modification of phenytoin clearance by valproic acid in normal subjects.

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