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The Pharmacokinetics of Antipyrine and Three of Its Metabolites in the Rabbit: Intravenous Administration of Pure Metabolites

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Abstract

Antipyrine (AP) is a commonly used probe of oxidative metabolism. Indirect evidence demonstrates formation rate limited disposition of its metabolites. Kinetic studies using antipyrine and its major metabolites 3-hydroxymethylantipyrine (HMA), norantipyrine (NORA), and 4-hydroxyantipyrine (OHA) were completed to investigate the metabolic fate of preformed antipyrine metabolite and to demonstrate directly formation rate-limited metabolite disposition in vivo. Bolus injections of antipyrine and preformed metabolites (40-50 mg/kg) were administered to male, New Zealand white rabbits. Plasma and urine were analyzed using HPLC. These studies demonstrate that HMA, NORA, and OHA are formation rate limited in the rabbit. NORA appears to undergo further extensive oxidative and conjugative metabolism. Unknown additional peaks were detected in urine after NORA dosing but not after HMA or OHA administration. Mass spectroscopy of the unknown HPLC eluents identified potential structures of these NORA metabolites.

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Authors and Affiliations

  1. The Drug Evaluation Unit, Department of Medicine, Division of Nephrology, Hennepin County Medical Center, Minneapolis, Minnesota, 55415

    John V. St. Peter

  2. College of Pharmacy, University of Minnesota, Minneapolis, Minnesota, 55455

    John V. St. Peter, Yusuf Abul-Hajj & Walid M. Awni

  3. The Drug Evaluation Unit, Department of Medicine, Division of Nephrology, Hennepin County Medical Center, Minneapolis, Minnesota, 55415

    Walid M. Awni

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  1. John V. St. Peter
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  2. Yusuf Abul-Hajj
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  3. Walid M. Awni
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St. Peter, J.V., Abul-Hajj, Y. & Awni, W.M. The Pharmacokinetics of Antipyrine and Three of Its Metabolites in the Rabbit: Intravenous Administration of Pure Metabolites. Pharm Res 8, 1470–1476 (1991). https://doi.org/10.1023/A:1015830013451

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