Kinetics and metabolism of fomepizole in healthy humans

Clinical Toxicology : the Official Journal of the American Academy of Clinical Toxicology and European Association of Poisons Centres and Clinical Toxicologists
K E McMartinDag Jacobsen

Abstract

Fomepizole, a potent inhibitor of alcohol dehydrogenase, has replaced ethanol as antidote for methanol and ethylene glycol intoxications because of a longer duration of action and fewer adverse effects. Prior human studies have indicated that single doses of fomepizole are eliminated by Michaelis-Menten kinetics, but two studies in poisoned patients have suggested that first order elimination occurs after multiple doses. Because of the contrast in fomepizole kinetics among existing studies and the lack of information regarding its metabolism in humans, kinetic and metabolic studies were conducted after single doses and after multiple oral doses in healthy human subjects. In a single-dose, crossover study, healthy humans received fomepizole IV or orally (7 mg/kg). Also to define the metabolism and kinetics of fomepizole when administered over the presumed antidotal period, subjects were divided into three groups, which were given oral loading doses of 10-15 mg/kg, followed by supplemental doses of 3-10 mg/kg/12 h through 96 hours. The single dose study confirmed that fomepizole was eliminated by saturable, nonlinear kinetics, primarily by metabolism, and subsequent renal excretion of the metabolite 4-carboxypyrazole (4-CP). In t...Continue Reading

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Citations

Jul 18, 2014·PloS One·Anastasia V ShindyapinaYuri L Dorokhov
Aug 16, 2012·Clinical Toxicology : the Official Journal of the American Academy of Clinical Toxicology and European Association of Poisons Centres and Clinical Toxicologists·Rebeca GraciaKenneth E McMartin
Jun 27, 2015·Clinical Toxicology : the Official Journal of the American Academy of Clinical Toxicology and European Association of Poisons Centres and Clinical Toxicologists·Jeffrey A Kraut
Dec 9, 2014·PloS One·Deep PandyaCristiano Ferlini
Nov 10, 2015·British Journal of Clinical Pharmacology·Kenneth McMartinKnut Erik Hovda
Mar 14, 2019·Mini Reviews in Medicinal Chemistry·Miroslav Pohanka
Sep 30, 2021·Clinical Toxicology : the Official Journal of the American Academy of Clinical Toxicology and European Association of Poisons Centres and Clinical Toxicologists·Yvonne E LaoKnut Erik Hovda
Nov 14, 2021·Human & Experimental Toxicology·Omid MehrpourChristopher Hoyte

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