Increased plasma fatty acid ethyl ester levels following inhibition of oxidative metabolism of ethanol by 4-methylpyrazole treatment in human subjects

Alcohol Clin Exp Res. 2006 Jul;30(7):1126-31. doi: 10.1111/j.1530-0277.2006.00138.x.


Background: Recent experimental evidence suggests that fatty acid ethyl esters (FAEE), nonoxidative metabolites of ethanol, mediate ethanol-induced organ damage. A direct association between pancreas-specific toxicity and increased levels of FAEE following inhibition of the oxidative metabolism of ethanol by 4-methylpyrazole (4-MP) has previously been shown in studies with rats.

Methods: We obtained plasma samples from 32 healthy human volunteers who drank ethanol following 4-MP or placebo ingestion to determine whether in vivo inhibition of oxidative metabolism of ethanol causes a shift to nonoxidative metabolism of ethanol and the subsequent production of increased levels of FAEE. Plasma FAEE were isolated by solid-phase extraction and quantified by gas chromatography-mass spectrometry (GC-MS).

Results: Plasma FAEE levels in subjects receiving 4-MP treatment before ethanol consumption were elevated compared with plasma FAEE concentrations taken from control subjects who received a placebo before ethanol ingestion. Increased FAEE levels in the 4-MP treatment group occurred after peak blood ethanol, and peak FAEE levels were achieved. There was a correlation between the blood ethanol and the plasma FAEE levels, and the correlation persisted in the presence or absence of 4-MP. The peak FAEE values were greater in men than in women, with or without 4-MP treatment.

Conclusions: Our results indicate that the in vivo inhibition of the oxidative metabolism of ethanol using 4-MP results in an increased circulating concentration of FAEE, products of the nonoxidative metabolism of ethanol.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Antidotes / pharmacology*
  • Double-Blind Method
  • Esters / blood*
  • Ethanol / blood*
  • Fatty Acids / blood*
  • Female
  • Fomepizole
  • Humans
  • Male
  • Oleic Acids / blood
  • Oxidation-Reduction / drug effects*
  • Pyrazoles / pharmacology*
  • Time Factors


  • Antidotes
  • Esters
  • Fatty Acids
  • Oleic Acids
  • Pyrazoles
  • Ethanol
  • Fomepizole
  • ethyl oleate