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Effects of 4-methylpyrazole, methanol/ethylene glycol antidote, in healthy humans.

Abstract
4-Methylpyrazole (4-MP), an inhibitor of alcohol dehydrogenase, may be useful for the treatment of methanol and ethylene glycol intoxications. A placebo-controlled, double blind, multiple dose, sequential, ascending-dose study has been performed to determine the tolerance of 4-MP in healthy volunteers. Oral loading doses of 4-MP were followed by supplemental doses every 12 h through 5 days, producing plasma levels in the therapeutic range. A slight, transient elevation in one or both serum transaminase values was observed in 6 of the 15 subjects treated with 4-MP. This effect was not dose related nor apparently mediated through a hypersensitivity reaction. Serum triglyceride levels were increased in 30% of 4-MP treated subjects, but also in 25% of the placebo subjects. 4-MP treatment did not produce any other significant changes in objective clinical parameters nor in subjective side effects. 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. Nevertheless, the slower elimination rate and lesser degree of toxicity of 4-MP would make it preferable to ethanol in therapy of these poisonings.
AuthorsD Jacobsen, C S Sebastian, S K Barron, E W Carriere, K E McMartin
JournalThe Journal of emergency medicine (J Emerg Med) 1990 Jul-Aug Vol. 8 Issue 4 Pg. 455-61 ISSN: 0736-4679 [Print] United States
PMID2212566 (Publication Type: Clinical Trial, Controlled Clinical Trial, Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Ethylene Glycols
  • Pyrazoles
  • Fomepizole
  • Alcohol Dehydrogenase
  • Methanol
Topics
  • Adult
  • Alcohol Dehydrogenase (antagonists & inhibitors)
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Ethylene Glycols (metabolism, poisoning)
  • Fomepizole
  • Humans
  • Male
  • Methanol (metabolism, poisoning)
  • Poisoning (drug therapy)
  • Pyrazoles (administration & dosage, adverse effects, therapeutic use)

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