Non-Linear Formation of EtG and FAEEs after Controlled Administration of Low to Moderate Doses of Ethanol

作者：Perez Mana Clara; Farre Magi^*; Pastor Antoni; Fonseca Francina; Torrens Marta; Menoyo Esther; Pujadas Mitona; Frias Silvia; Langohr Klaus; de la Torre Rafael

来源：Alcohol and Alcoholism, 2017, 52(5): 587-594.

DOI：10.1093/alcalc/agx033

Aims: Ethyl glucuronide (EtG) and fatty acid ethyl esters (FAEEs) are non-oxidative metabolites of alcohol that can be detected in conventional and non-conventional biological matrices for longer periods than alcohol. The aim was to describe the time courses of both biomarkers after ingestion of acute low-moderate doses of ethanol.
Methods: The study design was double-blind, randomized, crossover and controlled with placebo. Participants were distributed in three different cohorts: (a) Cohort-1: two doses of 18 and 30 g of ethanol and placebo were administered to 12 subjects; (b) Cohort-2: two doses of 6 and 12 g of ethanol and placebo were administered to six subjects and (c) Cohort-3: two doses of 24 and 42 g of ethanol and placebo were administered to six subjects. Each participant received two doses of ethanol and placebo. Plasma concentrations (0-6 h) of ethanol and specific FAEEs (palmitic, stearic, linoleic and oleic acid ethyl esters) and urinary concentrations of EtG (0-24 h) were measured.
Results: A dose-dependent increase in blood ethanol concentrations was observed. EtG excretion and FAEEs plasmatic concentrations showed a disproportionate increase with the ethanol dose suggesting non-linearity. Area under the curve (AUC(0-6h)) of ethanol concentrations showed a linear trend with non-oxidative metabolites' concentrations.
Conclusion: The formation rate of ethanol non-oxidative biomarkers does not follow a linear trend, explained mainly by a disproportionate increase in AUC(0-6 h) of ethanol concentrations in relation to dose. This observation should be taken into account when interpreting results in biological matrices in clinical and forensic settings.
Short summary: A double-blind, randomized, crossover and controlled study was conducted administering ethanol (6-42 g). Ethyl glucuronide (EtG) excretion and fatty acid ethyl esters (FAEEs) plasmatic concentrations showed a disproportionate increase with the ethanol dose suggesting non-linearity. This observation should be taken into account when interpreting biomarker concentrations in clinical settings.

• 出版日期2017-9