Inhibition of drug metabolism by hydroxylated metabolites: cross-inhibition and specificity

Inhibition of drug metabolism was studied in adult male Sprague-Dawley rats. A hydroxylated metabolite of phenylbutazone (oxyphenbutazone) inhibited the elimination of phenytoin, which is metabolized by oxidative pathways. The biotransformation of a relatively polar and only slightly plasma protein-...

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Bibliographic Details
Published inJournal of pharmaceutical sciences Vol. 64; no. 12; p. 1928
Main Authors Soda, D M, Levy, G
Format Journal Article
LanguageEnglish
Published United States 01.12.1975
Subjects
Animals
Antipyrine - metabolism
Biotransformation
Depression, Chemical
Half-Life
Hydroxylation
Male
Oxidation-Reduction
Oxyphenbutazone - metabolism
Pharmaceutical Preparations - metabolism
Phenytoin - metabolism
Rats
Sulfanilamides - metabolism
Time Factors
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Summary:Inhibition of drug metabolism was studied in adult male Sprague-Dawley rats. A hydroxylated metabolite of phenylbutazone (oxyphenbutazone) inhibited the elimination of phenytoin, which is metabolized by oxidative pathways. The biotransformation of a relatively polar and only slightly plasma protein-bound drug, antipyrine, was subject to product inhibition by a hydroxylated metabolite, 4-hydroxyantipyrine. Neither oxyphenbutazone nor 4-hydroxyantipyrine measurably affected the elimination kinetics or metabolic fate of a drug (sulfanilamide) that is not metabolized by oxidative pathways.
ISSN:0022-3549
DOI:10.1002/jps.2600641203