Fomepizole for the Treatment of Methanol Poisoning
New England Journal of MedicinePublished 8 February 2001Open access
Jeffrey Brent, Kenneth E. McMartin, Scott Phillips, Cynthia K. Aaron, Ken Kulig
Citations400
SJR quartileQ1
SJR score19.08
SNIP13.47
Generate an AI Snapshot to get a quick, structured summary of this paper.
Study Snapshot
ObjectiveStudy objective
MethodsResearch methodology
PopulationPopulation studied
Sample sizeSample sizes
OutcomesStudy outcomes here
ResultsStudy results comes here
LimitationsResearch study limitations comes here
A concise AI-generated summary of the paper will appear here once you click Generate AI Snapshot.
TL;DR
Fomepizole appears to be safe and effective in the treatment of methanol poisoning and nine patients survived and two patients who died had anoxic brain injury that was present at the time of enrollment.
Abstract
Fomepizole appears to be safe and effective in the treatment of methanol poisoning.
Keywords
Medicine
New England Journal of MedicineFomepizole for the Treatment of Ethylene Glycol Poisoning
358 Citations1999Jeffrey Brent, Kenneth E. McMartin +5 more
In patients with ethylene glycol poisoning, fomepizole administered early in the course of intoxication prevents renal injury by inhibiting the formation of toxic metabolites.
The American Journal of Emergency Medicine1998 annual report of the American association of poison control centers toxic exposure surveillance system
277 Citations1999Toby Litovitz, Wendy Klein‐Schwartz +4 more
Journal of Biological ChemistryFormaldehyde Dehydrogenase from Human Liver
218 Citations1974Lasse Uotila, Martti Koivusalo
S-Formylglutathione rather than formate is formed from formaldehyde and reduced glutathione in the reaction catalyzed by purified formaldehyde dehydrogenase, which is not strictly NAD-specific; NADP can be used although NADP has a much higher Km value than NAD, especially at high pH values.
Toxicology and Applied PharmacologyMethanol poisoning: Ocular toxicity produced by formate
209 Citations1978G. Martin‐Amat, Kenneth E. McMartin +3 more
Experiments were designed to study the possible role of formate in ocular toxicity and results were similar to those described for methanol poisoning: optic disc Edema with a normal vascular bed and intracellular edema with intraaxonal swelling.
Journal of Toxicology Clinical ToxicologyAntidotes for Methanol and Ethylene Glycol Poisoning
196 Citations1997Dag Jacobsen, Kenneth E. McMartin
Biochemical MedicineMethanol poisoning I. The role of formic acid in the development of metabolic acidosis in the monkey and the reversal by 4-methylpyrazole
186 Citations1975Kenneth E. McMartin, A.B. Makar +3 more
The use of the monkey as a model for the study of methanol poisoning is presented, and the possible use of 4-methylpyrazole in the treatment of metanol poisoning is implicit.
Acta Medica ScandinavicaFormate Concentrations in Plasma from Patients Poisoned with Methanol
137 Citations1983Ole M. Sejersted, Dag Jacobsen +2 more
It is concluded that formate accumulation is the main or only reason for acidosis in the early, uncomplicated stages of methanol poisoning and lactate may appear at more advanced stages.
Toxicology and Applied PharmacologyExperimental methanol toxicity in the primate: Analysis of metabolic acidosis
137 Citations1975Keith L. Clay, Robert C. Murphy +1 more
Of these animals, only the pigtail monkey reliably developed a severe metabolic organic acidosis resembling that observed in humans, and systemic formate concentrations remained low in rats and monkeys which failed to become acidotic following methanol administration.
Journal of Toxicology Clinical Toxicology4-Methylpyrazole may be an alternative to ethanol therapy for ethylene glycol intoxication in man
109 Citations1986Frédéric J. Baud, C Bismuth +5 more
It is suggested that 4 MP may decrease the metabolic consequences of EG poisoning in man and may be of therapeutic value when administered early during the course of the intoxication before coma, seizures and organic renal failure have occurred.
The LancetFomepizole in treatment of uncomplicated ethylene glycol poisoning
96 Citations1999Stephen W. Borron, Bruno Mégarbane +1 more
Fomepizole is an effective alternative to ethanol in the treatment of ethylene glycol poisoning and in a series of 38 acute poisonings without renal failure, fome pizole obviated the need for haemodialysis.
Archives of Biochemistry and BiophysicsStudies on the metabolic interactions between 4-methylpyrazole and methanol using the monkey as an animal model
95 Citations1980Kenneth E. McMartin, Karl‐Goran Hedström +3 more
4-methylpyrazole repeatedly injected in various dose combinations was able to reverse methanol toxicity in the monkey, indicating the usefulness of the monkey as a model to study 4-methyl pyrazole activity and toxicity in light of its possible use to treat methanl poisoning in man.
Journal of Chromatographic ScienceSimultaneous Determination of Lower Alcohols, Acetone and Acetaldehyde in Blood by Gas Chromatography
82 Citations1969ReneéH. Baker, A. L. Alenty +1 more
Alcoholism Clinical and Experimental Research4‐Methylpyrazole: A Controlled Study of Safety in Healthy Human Subjects after Single, Ascending Doses
75 Citations1988Dag Jacobsen, Cherian Sebastian +2 more
It is concluded that at a single dose of 4- MP (10-20 mg/kg) producing plasma levels within a probable therapeutic range, no side-effects were attributed to 4-MP.
Journal of Emergency MedicineEffects of 4-methylpyrazole, methanol/ethylene glycol antidote, in healthy humans
74 Citations1990Dag Jacobsen, Cherian Sebastian +3 more
The results suggest that a mild, transient increase in liver function tests might be observed in some subjects treated with multiple doses of 4-MP, which would make it preferable to ethanol in therapy of these poisonings.
Journal of Studies on AlcoholVariability in blood alcohol concentrations. Implications for estimating individual results.
69 Citations1983Blair J. O’Neill, Alan F. Williams +1 more
In a carefully controlled drinking situation there was great individual variation in peak blood alcohol concentrations (BACS) for given doses of alcohol, and alcohol nomograms and tables based on average results from such studies could be misleading.
Annals of Emergency MedicineTreatment of Methanol Poisoning With Intravenous 4-Methylpyrazole
66 Citations1997Michael J. Burns, Andis Graudins +3 more
Clinical and toxicokinetic data of a patient with methanol poisoning who was treated with fomepizole are reported, showing that formic acid levels remained undetectable during fome pizole treatment, the toxic effects of methnol were prevented, and the patient made a full recovery.
Proceedings of the National Academy of SciencesPyrazoles as inhibitors of alcohol oxidation and as important tools in alcohol research: An approach to therapy against methanol poisoning
66 Citations1979Rolf Blomstrand, Helene Östling-Wintzell +4 more
4-Methylpyrazole, at a level in the plasma of more than 10 muM, prevented accumulation of the toxic metabolite formic acid in methanol-poisoned monkeys, and repeated injections of 4-methylpyrazoles abolished methanl toxicity in monkeys receiving lethal doses of methanols.
Archives of Biochemistry and BiophysicsBiological effects and metabolic interactions after chronic and acute administration of 4-methylpyrazole and ethanol to rats
64 Citations1980Rolf Blomstrand, Åke Ellin +2 more
The present investigation has shown that the acute and chronic toxicity of 4-methylpyrazole alone or in combination with ethanol is minimal at doses that are effective in blocking ethanol metabolism in the rat.
Journal of Toxicology Clinical Toxicology4-Methylpyrazole and Hemodialysis in Ethylene Glycol Poisoning
57 Citations1996Eric Jobard, P. Harry +3 more
Filtration of a 4-methylpyrazole loading dose of 10-20 mg/kg before dialysis and intravenous infusion of 1-1.5 mg/ kg/h during the 8-12 hours of hemodialysis to compensate the loss in dialysate are proposed.
Naunyn-Schmiedeberg s Archives of PharmacologyChronopharmacokinetics of ethanol
50 Citations1976F. M. Sturtevant, Ruthann P. Sturtevant +2 more
Preliminary results suggest that pharmacokinetic parameters may not be invariable with time of day, and appear to exhibit circadian rhythmicity.
Journal of Analytical ToxicologyGas Chromatographic Analysis of Methyl Formate and Application in Methanol Poisoning Cases
40 Citations1989Albert D. Fraser, Wallace MacNeil
Formate analysis is considered important in any patient with suspected methanol poisoning who presents for medical assistance with metabolic acidosis, because the extent of ocular toxicity correlates better with formate concentration than with methnol concentration.
Biochemical MedicineGas chromatographic head-space assay of formic acid as methyl formate in biologic fluids: Potential application to methanol poisoning
38 Citations1980Craig Abolin, John D. McRae +2 more
A rapid, sensitive gas chromatographic head-space method was developed for assay of biologic fluids for formic acid by its conversion to methyl formate and has potential application to methanol poisoning.
Intensive Care MedicineTwo cases of acute methanol poisoning partially treated by oral 4-methylpyrazole
34 Citations1999Philippe Hantson, Pierre Wallemacq +4 more
Two cases of acute methanol intoxication partially treated by this potent alcohol dehydrogenase (ADH) inhibitor are reported, and the use of 4-MP is better documented in cases of ethylene glycol poisoning and could also become an accepted option for the management of meethanol poisoning.
Drug and Alcohol DependenceStudies on the effect of 4-methylpyrazole on methanol poisoning using the monkey as an animal model: With particular reference to the ocular toxicity
28 Citations1984Rolf Blomstrand, Sven‐Olof Ingemansson
Young cynomolgus monkeys were chosen as a model to investigate the ocular toxicity in animals poisoned with methanol and treated with 4-methylpyrazole and showed no signs of toxicity on ocular examinations which included ophtalmoscopy and electroretinogram (ERG) recordings.
Drug and Alcohol DependenceNormal electroretinogram and no toxicity signs after chronic and acute administration of the alcohol dehydrogenase inhibitor 4-methylpyrazole to the cynomolgus monkey (Macaca fascicularis) — A possible new treatment of methanol poisoning
27 Citations1984Rolf Blomstrand, Sven‐Olof Ingemansson +2 more
Because of the low toxicity of 4-MP and its powerful inhibitory capacity on alcohol dehydrogenase, the substance should prove a potential tool in clinical alcohol research and an effective antidote in clinical situations where inhibition of alcohol dehydration is the key to a successful outcome of, for example, methanol and ethylene glycol poisoning.
Journal of Toxicology Clinical ToxicologyFomepizole (4-Methylpyrazole) in Fatal Methanol Poisoning with Early CT Scan Cerebral Lesions
26 Citations1999Christophe Girault, Fabienne Tamion +5 more
The fomepizole treatment protocol was simple to use and appeared effective in eliminating methanol in combination with hemodialysis and the early onset of cerebral lesions demonstrated by computed tomography (CT) scan.
Acta Pathologica Microbiologica Scandinavica Section A PathologyLONG TERM TOXICITY STUDY WITH ALCOHOL AND 4‐METHYLPYRAZOLE IN RAT
26 Citations1974Lars Kager, Jan L. E. Ericsson
It is concluded that further investigations are needed before 4-methylpyrazole can be used in adequate repeated doses in clinical investigations in man.
Journal of Toxicology Clinical ToxicologyHigh Pressure Liquid Chromatographic Assay of 4-Methylpyrazole. Measurements of Plasma and Urine Levels
20 Citations1984Kenneth E. McMartin, Timothy D. Collins +1 more
An HPLC assay has been developed to measure 4- MP levels in plasma and urine samples and has practical application for research laboratories dealing with ethanol metabolism and clinical laboratories desiring to monitor 4-MP levels.
Biomedical ChromatographyDetermination of 4‐methylpyrazole in plasma using solid phase extraction and HPLC
14 Citations1987Ulf Diczfalusy, R. Eklöf
A rapid method for the determination of 4-methylpyrazole in plasma is described and it is found that the sensitivity is sufficient for analysis of plasma levels in the low micromolar range.