American College of Medical Toxicology.Objective. Fomepizole elimination in poisoned patients at therapeutic plasma concentrations appears be similar to that reported previously in healthy human subjects.Ĥ-Methylpyrazole Ethylene glycol poisoning Methanol poisoning Pharmacokinetics Zero-order elimination. Plasma concentrations during the repeated dosing confirmed that the recommended dosing schedule, with and without intermittent hemodialysis, maintained therapeutic concentrations throughout the treatments. Elimination during intermittent hemodialysis followed first-order kinetics, with a half-life of 3 h. Zero-order elimination rates averaged 13 and 17 μmol/L/h in methanol and ethylene glycol patients, respectively, compared to 6-19 μmol/L/h in healthy subjects. In healthy human subjects, fomepizole elimination follows Michaelis-Menten kinetics and has been calculated as zero-order elimination rates. After repeated doses of fomepizole, the minimum trough concentration averaged 86-109 µmol/L, which is 10 times higher than the minimum therapeutic concentration. In methanol- and ethylene glycol-poisoned patients, fomepizole had a volume of distribution of 0.66-0.68 L/kg. The elimination of fomepizole was assessed after individual doses, both during and without intermittent hemodialysis. Plasma samples from 26 patients in the clinical trials of the use of fomepizole for methanol and ethylene glycol poisoning were analyzed for fomepizole concentrations. This study was designed to relate the elimination of fomepizole in a series of poisoned patients to that in healthy humans. Although its elimination kinetics have been well described in healthy human subjects, the elimination in poisoned patients have only been described in a few isolated cases. Fomepizole is an anti-metabolite therapy that is used to diminish the toxicity from methanol or ethylene glycol.
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