Fomepizole for the treatment of methanol poisoning.
BACKGROUND
Methanol poisoning may result in metabolic acidosis, blindness, and death. The inhibition of alcohol dehydrogenase is fundamental to the treatment of methanol poisoning. We performed a multicenter study to evaluate fomepizole, an inhibitor of alcohol dehydrogenase, in the treatment of patients with methanol poisoning.


METHODS
We administered intravenous fomepizole to 11 consecutive patients who presented with methanol poisoning at a participating center. Serial clinical and laboratory studies, including measurements of plasma formic acid and fomepizole, were performed. The outcomes measured were the preservation of visual acuity, the resolution of metabolic acidosis, the inhibition of formic acid production, the achievment of therapeutic plasma concentrations of fomepizole with the dosing regimen, residual illness or disability, and death.


RESULTS
Plasma formic acid concentrations were detectable in eight patients, and these concentrations were closely correlated with the initial arterial pH values (r=0.92, P<0.001). In response to fomepizole, plasma formic acid concentrations fell and metabolic abnormalities resolved in all patients. Nine patients survived. Seven patients initially had visual abnormalities, but at the end of the trial no surviving patient had any detectable visual deficits related to methanol poisoning. Fomepizole had few adverse effects. The two patients who died had anoxic brain injury 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 the treatment of methanol poisoning.
Brent
J
J
Toxicology Associates, and Division of Emergency Medicine, University of Colorado Health Sciences Center, Denver 80210, USA. jeffrey.brent@uchsc.edu
McMartin
K
K
Phillips
S
S
Aaron
C
C
Kulig
K
K
D000138:Acidosis / Q000188:drug therapy / Q000209:etiology; D000293:Adolescent; D000328:Adult; D000426:Alcohol Dehydrogenase / Q000037:antagonists & inhibitors*; D000931:Antidotes / Q000009:adverse effects / Q000627:therapeutic use*; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005260:Female; D000077604:Fomepizole; D005561:Formates / Q000097:blood; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D000432:Methanol / Q000097:blood / Q000506:poisoning*; D008875:Middle Aged; D011041:Poisoning / Q000188:drug therapy; D011446:Prospective Studies; D011720:Pyrazoles / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*
D000931:Antidotes; D004791:Enzyme Inhibitors; D005561:Formates; D011720:Pyrazoles; C030544:formic acid; D000077604:Fomepizole; D000426:Alcohol Dehydrogenase; D000432:Methanol