Fomepizole for the Treatment of Methanol Poisoning
Jeffrey Brent, M.D., Ph.D., Kenneth McMartin, Ph.D., Scott Phillips, M.D., Cynthia Aaron, M.D., Ken Kulig, M.D., for The Methylpyrazole for Toxic Alcohols Study Group
Background Methanol poisoning may result in metabolic acidosis,blindness, and death. The inhibition of alcohol dehydrogenaseis fundamental to the treatment of methanol poisoning. We performeda multicenter study to evaluate fomepizole, an inhibitor ofalcohol dehydrogenase, in the treatment of patients with methanolpoisoning.
Methods We administered intravenous fomepizole to 11 consecutivepatients who presented with methanol poisoning at a participatingcenter. Serial clinical and laboratory studies, including measurementsof plasma formic acid and fomepizole, were performed. The outcomesmeasured were the preservation of visual acuity, the resolutionof metabolic acidosis, the inhibition of formic acid production,the achievement of therapeutic plasma concentrations of fomepizolewith the dosing regimen, residual illness or disability, anddeath.
Results Plasma formic acid concentrations were detectable ineight patients, and these concentrations were closely correlatedwith the initial arterial pH values (r=0.92, P<0.001). Inresponse to fomepizole, plasma formic acid concentrations felland metabolic abnormalities resolved in all patients. Nine patientssurvived. Seven patients initially had visual abnormalities,but at the end of the trial no surviving patient had any detectablevisual deficits related to methanol poisoning. Fomepizole hadfew adverse effects. The two patients who died had anoxic braininjury that was present at the time of enrollment. During treatment,methanol had an elimination half-life of 54 hours.
Conclusions Fomepizole appears to be safe and effective in thetreatment of methanol poisoning.
Source Information
From Toxicology Associates (J.B., S.P., K.K.), the Section of Clinical Pharmacology and Toxicology (J.B., S.P.), the Division of Emergency Medicine (J.B., K.K.), and the Section of Pediatric Pharmacology (J.B., K.K.), University of Colorado Health Sciences Center, Denver; the Department of Pharmacology, Louisiana State University Medical Center, Shreveport (K.M.); and the Department of Emergency Medicine, University of Massachusetts Medical Center, Worcester (C.A.).
Address reprint requests to Dr. Brent at Toxicology Associates, 2555 S. Downing, Suite 260, Denver, CO 80210, or at jeffrey.brent{at}uchsc.edu.
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