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Antipyrine as a Model Drug Substance to Assess Oxidative Metabolism

Peter K. Konig, MD; Louis Cantilena, MD, PhD
Arch Intern Med. 1994;154(5):590. doi:10.1001/archinte.1994.00420050162015.
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We read with interest the article by Crussell-Porter et al1 on the effect of low-dose fluconazole on the effect of warfarin. We agree with the conclusion of the authors that close monitoring of prothrombin times is recommended during concomitant therapy with fluconazole. Our division demonstrated a similar effect on the pharmacokinetics of terfenadine by fluconazole.2 We do, however, disagree with the authors' statement that the inhibitory effects of fluconazole are minimal because it does not alter the disposition of antipyrine in humans. While it is true that antipyrine has traditionally been considered a model drug for evaluating drug metabolizing capacity,3 hepatic oxidative metabolism involves numerous P450 subfamilies, all of which do not necessarily contribute to the metabolism of antipyrine.4 That is to say, antipyrine metabolism may be affected differently from warfarin5 or even unaffected by well-known inhibitors of drug metabolism,6 including ketoconazole.7,8 For


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