title: Increased plasma fatty acid ethyl ester levels following inhibition of oxidative metabolism of ethanol by 4-methylpyrazole treatment in human subjects.
abstract: 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.
authors.affiliation: Department of Pathology, Division of Laboratory Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Best
authors.forename: Taisto
authors.initials: T
authors.lastname: Sarkola
authors.forename: C J Peter
authors.initials: CJ
authors.lastname: Eriksson
authors.forename: Joanne E
authors.initials: JE
authors.lastname: Cluette-Brown
authors.forename: Michael
authors.initials: M
authors.lastname: Laposata
mesh_terms: D000328:Adult; D000931:Antidotes / Q000494:pharmacology*; D004311:Double-Blind Method; D004952:Esters / Q000097:blood*; D000431:Ethanol / Q000097:blood*; D005227:Fatty Acids / Q000097:blood*; D005260:Female; D000077604:Fomepizole; D006801:Humans; D008297:Male; D009829:Oleic Acids / Q000097:blood; D010084:Oxidation-Reduction / Q000187:drug effects*; D011720:Pyrazoles / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D000931:Antidotes; D004952:Esters; D005227:Fatty Acids; D009829:Oleic Acids; D011720:Pyrazoles; D000431:Ethanol; D000077604:Fomepizole; C033180:ethyl oleate