TY - JOUR
T1 - Effects of 4-methylpyrazole, methanol/ethylene glycol antidote, in healthy humans
AU - Jacobsen, Dag
AU - Sebastian, C. Simon
AU - Barron, Susan K.
AU - Carriere, Edward W.
AU - McMartin, Kenneth E.
N1 - Funding Information:
Acknowledgments - Supported by FDA Orphan Product Development Grants FDR-000114 and FDR-000292 and by Fogarty International Research Fellowship TWO-03763. We would also like to thank Sharon Farrar for preparation of the manuscript and Dianne Cox, R.N., for technical assistance.
PY - 1990
Y1 - 1990
N2 - 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.
AB - 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.
KW - 4-methylpyrazole
KW - antidote
KW - clinical toxicology study
KW - ethylene glycol poisoning
KW - methanol poisoning
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U2 - 10.1016/0736-4679(90)90176-V
DO - 10.1016/0736-4679(90)90176-V
M3 - Article
C2 - 2212566
AN - SCOPUS:0024992883
SN - 0736-4679
VL - 8
SP - 455
EP - 461
JO - Journal of Emergency Medicine
JF - Journal of Emergency Medicine
IS - 4
ER -