Phosphatidylethanol and Other Ethanol Consumption Markers

磷脂酰乙醇和其他乙醇消耗标志物

• 批准号: 8562032
• 负责人: Donald M Dougherty
• 金额: $ 48.89万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-20 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8562032
• 关键词: Abstinence; Address; Alcohol consumption; Alcoholic beverage heavy drinker; Alcohols; Biochemical; Biological Markers; Blood; Cause of Death; Characteristics; Clinic Visits; Clinical; Detection; Dose; Drug Kinetics; Erythrocytes; Ethanol; Foundations; Future; Goals; Guidelines; Half-Life; Heavy Drinking; Individual; Laboratories; Light; Methods; Patient Self-Report; Pattern; Phospholipids; Prevention program; Recruitment Activity; Relative (related person); Role; Sampling; Series; Specificity; Technology; United States; Urine; Woman; Work; alcohol exposure; alcohol monitoring; clinically significant; drinking; innovation; men; monitoring device; phosphatidylethanol; public health relevance; treatment program

DESCRIPTION (provided by applicant): The overall goal of this study is to characterize the pharmacokinetics of synthesis and elimination of phosphatidylethanol as an alcohol-use biomarker in a laboratory setting, and then to determine its clinical utility alone and together wih other established biomarkers. We will use an innovative approach to objectively characterize alcohol use in the "real world" and use two recent advancements in the alcohol field: (1) transdermal alcohol monitoring devices and the refinement of methods that can objectively quantify alcohol use; and (2) the recent characterization of the biochemical metabolite of ethanol called phosphatidylethanol, a phospholipid produced and stored in red blood cells. Phosphatidylethanol appears to have unique characteristics as a biomarker for alcohol consumption, including a longer window of detection (compared to other direct markers) and its high specificity for alcohol consumption (compared to indirect markers). We propose three studies to characterize and validate this marker. In Studies 1 and 2, we will characterize the synthesis and elimination of phosphatidylethanol after a single administration of alcohol and after a series of consecutively administrated doses of alcohol across days, respectively. These two studies will be conducted in groups of light (< 2 drinks/day for women and men) and heavy drinkers (e4 drinks/day for women and e5 for men), and two doses of alcohol will be used (0.4 or 0.8 g/kg). These studies will allow us to examine how phosphatidylethanol is synthesized after a single or multiple drinking episodes. In Study 3, light, moderate (2-3 drinks/day for women and 2-4 for men), and heavy drinkers will be recruited to wear transdermal alcohol monitoring devices for 28 days and be asked to drink as usual. They will visit the clinic weekly to provide blood and urine samples, which will be used to analyze phosphatidylethanol and other alcohol biomarkers. This last study will allow us to determine how PEth alone (and in combination with 3 other biomarkers) can be used to identify an individual's level and pattern of drinking. This study allows us to address three primary aims: to examine the pharmacokinetics of phosphatidylethanol synthesis and elimination following the administration of a single alcohol dose (either 0.4 or 0.8 g/kg) among light and heavy drinkers (Aim 1); to examine the pharmacokinetics of phosphatidylethanol synthesis, accumulation, and elimination during and after 5 consecutive days of alcohol administration (either 0.4 or 0.8 g/kg) among light and heavy drinkers (Aim 2); and to determine the utility of phosphatidylethanol to identify different pattern of drinking (i.e., light, moderate, or heavy) observed naturalistically and to identify how this relates to other biomarkers and/or may be used with other biomarkers to identify particular clinically significant patterns of alcohol use (Aim 3). These studies are critically important step in advancing the use of phosphatidylethanol as an alcohol-use biomarker, and in identifying its role relative to other biomarkers for identifying drinking patterns in the "real world".

描述(由申请人提供)：这项研究的总体目标是在实验室环境下表征作为酒精使用生物标记物的磷脂酰乙醇的合成和消除的药代动力学，然后单独和与其他已建立的生物标记物一起确定其临床用途。我们将使用一种创新的方法来客观地描述“现实世界”中的酒精使用情况，并使用酒精领域的两项最新进展：(1)经皮酒精监测设备和能够客观量化酒精使用的改进方法；以及(2)最近对乙醇的生化代谢产物磷脂酰乙醇的表征，磷脂是一种在红细胞中产生和储存的磷脂。作为酒精消费的生物标志物，磷脂酰乙醇似乎具有独特的特征，包括较长的检测窗口(与其他直接标志物相比)和对酒精消费的高度特异性(与间接标志物相比)。我们提出了三项研究来表征和验证这一标记。在研究1和研究2中，我们将分别描述单次给药和连续几天给药后磷脂酰乙醇的合成和消除情况。这两项研究将分成两组进行：轻度饮酒(女性和男性每天2杯)和重度饮酒者(女性每天喝e4杯，男性每天喝e5杯)，并使用两种剂量的酒精(0.4或0.8克/公斤)。这些研究将使我们能够研究在一次或多次饮酒后磷脂酰乙醇是如何合成的。在研究3中，轻度、中度(女性每天2-3杯，男性2-4杯)和重度饮酒者将被招募佩戴酒精透皮监测设备28天，并被要求照常饮酒。他们每周都会去诊所看病 提供血液和尿液样本，用于分析磷脂酰乙醇和其他酒精生物标志物。这最后一项研究将使我们能够确定如何单独使用PEH(以及与其他3个生物标记物一起)来识别个人的饮酒水平和模式。这项研究允许我们解决三个主要目标：研究单次酒精剂量(0.4或0.8 g/kg)在轻度饮酒者和重度饮酒者(目标1)中的磷脂酰乙醇合成和消除的药代动力学(目标1)；检测连续5天酒精摄入(0.4或0.8 g/kg)期间和之后(目标2)轻度饮酒者和重度饮酒者(目标2)中磷脂酰乙醇合成、积累和消除的药代动力学；以及确定磷脂酰乙醇对识别在自然界观察到的不同饮酒模式(即，轻度、中度或重度)的效用，并确定这与其他生物标记物和/或可与其他生物标记物一起用于识别特定的临床显著饮酒模式(目标3)。这些研究是推进磷脂酰乙醇作为酒精使用生物标记物的使用的关键一步，并确定其相对于其他生物标记物在确定“现实世界”饮酒模式方面的作用。