Biomarcadores del consumo de alcohol y su relación con la dosis.

Abstract

Introduction_x000D_ The detection of biomarkers of alcohol consumption is a useful tool to prevent_x000D_ the emergence of social and health problems related to alcohol intake. Alcohol_x000D_ consumption can be monitored by detecting biomarkers. Indirect biomarkers_x000D_ (mean corpuscular volume, transaminases, gammaglutamyltranspeptidase or_x000D_ carbohydrate-deficient transferrin) are used in common practice, although_x000D_ there are also direct biomarkers of alcohol consumption, including alcohol_x000D_ itself and its metabolites. The non-oxidative biomarkers of ethanol such as_x000D_ ethyl glucuronide (EtG), ethyl sulphate (EtS) and fatty acid ethyl esters_x000D_ (FAEEs) in different biological matrices provide better control of consumption._x000D_ In the same way, these metabolites have a longer elimination half-life than_x000D_ ethanol, which can be detected along days-hours, in relation to the amount of_x000D_ alcohol ingested and the specific metabolite. The aim of this thesis project is_x000D_ to know and carry out a more complete study of the relationship between_x000D_ alcohol dose and non-oxidative biomarker concentrations and to evaluate_x000D_ these in specific populations (low-risk adult consumers) from a gender_x000D_ perspective. Methods_x000D_ A single-blind, non-randomized, pharmacokinetic clinical trial was conducted_x000D_ on healthy, volunteers with one treatment condition per subject between of_x000D_ four possible, containing 20 g, 40 g, 60 g, and 80 g of alcohol. A total of 53_x000D_ subjects of both genders participated (15 for each dose of 20, 40 and 60 g,_x000D_ and 8 for the 80 g dose). For inclusion the participants were required to have_x000D_ an intake of at least 1 standar drink unit/day (accumulated weekly) and_x000D_ previous drunken experience. Blood concentrations of ethanol, ethyl_x000D_ glucuronide (EtG) and ethyl sulfate (EtS), and four FAEEs (palmitate,_x000D_ linoleate, oleate and stearate) were determined. EtG and EtS were_x000D_ determined in urine. Additionally, the physiological, subjective and tolerability_x000D_ effects of alcohol were determined. In addition, alcohol concentrations and_x000D_ their respective metabolites in plasma and urine were determined._x000D_ Physiological effects included measurement of blood pressure, heart rate and_x000D_ oral temperature._x000D_ The subjective effects of the different doses of alcohol were evaluated by_x000D_ several questionnaires such as visual analogue scales EAV, ARCI (Addiction_x000D_ Research Center Inventory-49 item short form, BAES (Bifasic Alcohol Effects_x000D_ Scale), VESSPA (Subjective Effects Assessment of Substances with Abuse_x000D_ Potential), and a dose identification questionnaire._x000D_ Results_x000D_ It was observed that the maximum concentration (Cmax) increased following a_x000D_ linear relationship, while the area under the curve (AUC) was not linear at high_x000D_ doses. The time periods for detection of non-oxidative biomarkers were longer_x000D_ than for alcohol. Statistically significant gender differences were found in the_x000D_ area under the curve of alcohol concentrations from 0 to 10h (AUC10h) being_x000D_ higher in women than in men for the 3 doses that were compared. In the_x000D_ urinary excretion of EtG and EtS it was observed that the increase in the AUC_x000D_ was greater as the dose of alcohol increased, in both genders, being detected the concentrations until 48h post-administration with high doses. There were_x000D_ considerable differences between individuals with different doses._x000D_ Conclusions_x000D_ The AUC of the different non-oxidative alcohol biomarkers (FAEEs, EtG and_x000D_ EtS) followed a non-linear relationship with the alcohol dose, in contrast to_x000D_ what was observed with the Cmax of alcohol. The metabolites of the (FAEEs,_x000D_ Etg and Ets) in plasma were detected until 10h post-administration, while in_x000D_ urine the metabolites of EtG and EtS were detected until 48 hours. Gender_x000D_ differences were found in both alcohol and metabolite concentrations and_x000D_ effects (generally higher in women).

Date of Award	11 Dec 2019
Original language	Spanish
Supervisor	Magi Farre Albaladejo (Director), Magi Farre Albaladejo (Tutor), Clara Perez Maña (Director), Maria Francina Fonseca Casals (Director) & Marta Torrens Melich (Director)