Effects of 4-methylpyrazole, methanol/ethylene glycol antidote, in healthy humans.
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.
Jacobsen
D
D
Department of Pharmacology, Louisiana State University Medical Center, Shreveport 71130-3932.
Sebastian
C S
CS
Barron
S K
SK
Carriere
E W
EW
McMartin
K E
KE
D000328:Adult; D000426:Alcohol Dehydrogenase / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005026:Ethylene Glycols / Q000378:metabolism / Q000506:poisoning; D000077604:Fomepizole; D006801:Humans; D008297:Male; D000432:Methanol / Q000378:metabolism / Q000506:poisoning; D011041:Poisoning / Q000188:drug therapy; D011720:Pyrazoles / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use
D005026:Ethylene Glycols; D011720:Pyrazoles; D000077604:Fomepizole; D000426:Alcohol Dehydrogenase; D000432:Methanol