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PMID: 383353 Published · ppublish English Journal Article Review

Clinical pharmacokinetics of phenytoin.

Clinical pharmacokinetics ·Vol. 4 ·No. 3 ·1979-00-00 ·Pages 153-69

Richens A

Abstract

Phenytoin is a relatively insoluble weak acid, usually administered as the sodium salt. Bioavailability is dependent upon particle size and problems of generic inequivalence have therefore arisen, particularly in Scandinavia. The drug has a moderately large volume of distribution and is approximately 90% bound to plasma proteins. Clinically important displacement can be caused by bilirubin and several drugs, particularly sodium valproate, which is often combined with phenytoin. Displacement will lower the total serum concentration but will little affect the free drug concentration. The metabolism of phenytoin to the major metabolite, 5-(p-hydroxyphenyl)-5-(phenylhydantoin, is saturable, giving rise to a non linear dose-serum concentration relationship. Therefore, the dose range compatible with a therapeutic serum concentration is narrow within subjects, and monitoring serum concentrations is of particular value in dosage tailoring. In renal failure, the binding of phenytoin to plasma proteins is reduced and therefore a lower range of serum drug concentrations is compatible with therapeutic control. In liver disease, binding may also be impaired but delayed metabolism may occur in addition. During pregnancy the serum concentration may fall progressively as pregnancy advances, probably due to an increased rate of metabolism. Phenytoin readily crosses the placenta, and is metabolised rapidly by the neonate exposed in utero.

MeSH Terms
Aged Blood Proteins/metabolism Epilepsy/drug therapy Female Humans Infant, Newborn Kidney Diseases/blood Kinetics Liver Diseases/blood Phenytoin/blood,metabolism,therapeutic use Protein Binding
Chemicals
Blood Proteins Phenytoin
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Richens A
References (104)
104 references, click to expand
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Article Info
Journal
Clinical pharmacokinetics
Abbr.
Clin Pharmacokinet
ISSN
0312-5963
DOI
10.2165/00003088-197904030-00001
Published
1979-00-00
Pages
153-69
Language
English
Region
Switzerland
NLM ID
7606849
Subset
IM
External Links
PubMed source DOI: 10.2165/00003088-197904030-00001 View journal details
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