Non-linear formation of EtG and FAEEs after controlled administration of low to moderate doses of ethanol

Pérez Mañá, Clara; Farré Albaladejo, Magí; Pastor, Antonio; Fonseca Casals, Francina, 1972-; Torrens, Marta; Menoyo Colomer, Esther; Pujadas Bastardes, Mitona; Frias, Silvia; Langohr, Klaus; Torre Fornell, Rafael de la

doi:http://dx.doi.org/10.1093/alcalc/agx033

Non-linear formation of EtG and FAEEs after controlled administration of low to moderate doses of ethanol

Citation

Pérez-Mañá C, Farré M, Pastor A, Fonseca F, Torrens M, Menoyo E et al. Non-Linear Formation of EtG and FAEEs after Controlled Administration of Low to Moderate Doses of Ethanol. Alcohol Alcohol. 2017 Sep 1;52(5):587-94. DOI: 10.1093/alcalc/agx033

Abstract

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 (AUC0-6h) 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 AUC0-6h 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.