Clara Pérez-Mañá1,2, Magí Farré2,3, Antoni Pastor1,2,4, Francina Fonseca2,5, Marta Torrens2,5, Esther Menoyo1, Mitona Pujadas1,4, Silvia Frias1, Klaus Langohr1,6, Rafael de la Torre1,4,7. 1. Integrative Pharmacology and Systems Neurosciences Research Group, Neurosciences Research Program, IMIM (Hospital del Mar Medical Research Institute), Doctor Aiguader 88, 08003 Barcelona, Spain. 2. Autonomous University of Barcelona (UAB), 08193 Cerdanyola del Vallès, Spain. 3. Department of Clinical Pharmacology, Hospital Universitari Germans Trias i Pujol-IGTP, Carretera de Canyet, s/n, 08916 Badalona, Spain. 4. CIBER de Fisiopatología Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Monforte de Lemos 3-5, 28029 Madrid, Spain. 5. Drug Addiction Unit, Institute of Neuropsychiatry and Addictions (INAD), IMIM, Parc de Salut Mar, Doctor Aiguader 88, 08003 Barcelona, Spain. 6. Department of Statistics and Operations Research, Universitat Politècnica de Cataluña (UPC)/BarcelonaTech, Jordi Girona 1-3, 08034 Barcelona, Spain. 7. Pompeu Fabra University (CEXS-UPF), Plaça de la Mercè 10-12, 08002 Barcelona, Spain.
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.
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.
Authors: Natalia Soldevila-Domenech; Anna Boronat; Julian Mateus; Patricia Diaz-Pellicer; Iris Matilla; Marta Pérez-Otero; Ana Aldea-Perona; Rafael de la Torre Journal: Nutrients Date: 2019-09-18 Impact factor: 5.717