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-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.
D000818:Animals; D000983:Antipyrine / Q000378:metabolism; D001711:Biotransformation; D003864:Depression, Chemical; D006207:Half-Life; D006900:Hydroxylation; D008297:Male; D010084:Oxidation-Reduction; D010113:Oxyphenbutazone / Q000378:metabolism; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010672:Phenytoin / Q000378:metabolism; D051381:Rats; D013424:Sulfanilamides / Q000378:metabolism; D013997:Time Factors
D004364:Pharmaceutical Preparations; D013424:Sulfanilamides; D010672:Phenytoin; D010113:Oxyphenbutazone; D000983:Antipyrine