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

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.Peer Reviewe