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（由申请方提供）：本研究的总体目标是在实验室环境中表征磷脂酰乙醇作为酒精使用生物标志物的合成和消除的药代动力学，然后确定其单独和与其他已确立的生物标志物一起的临床效用。我们将使用一种创新的方法来客观地表征“真实的世界”中的酒精使用，并使用酒精领域的两项最新进展：（1）透皮酒精监测设备和可以客观量化酒精使用的方法的改进;（2）最近对乙醇的生化代谢产物磷脂酰乙醇（一种在红细胞中产生和储存的磷脂）的表征。磷脂酰乙醇似乎具有独特的特征，作为酒精消费的生物标志物，包括较长的检测窗口（与其他直接标志物相比）及其对酒精消费的高特异性（与间接标志物相比）。我们提出了三项研究来表征和验证这个标记。在研究1和2中，我们将分别表征单次给予乙醇后和连续几天给予一系列剂量乙醇后磷脂酰乙醇的合成和消除。这两项研究将在轻度（女性和男性< 2杯/天）和重度饮酒者（女性e4杯/天，男性e5杯/天）中进行，并将使用两种剂量的酒精（0.4或0.8 g/kg）。这些研究将使我们能够检查磷脂酰乙醇是如何在一次或多次饮酒后合成的。在研究3中，将招募轻度、中度（女性2-3杯/天，男性2-4杯/天）和重度饮酒者佩戴经皮酒精监测装置28天，并要求他们照常饮酒。他们将每周访问诊所， 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。最后一项研究将使我们能够确定如何单独使用PEth（以及与其他3种生物标志物组合）来识别个体的饮酒水平和模式。这项研究使我们能够解决三个主要目标：检查磷脂酰乙醇的合成和消除后，单剂量酒精管理的药代动力学（0.4或0.8克/千克）（目标1）;为了检查磷脂酰乙醇合成，积累，在连续5天的酒精给药期间和之后的消除（0.4或0.8 g/kg）的影响（目的2）;并确定磷脂酰乙醇用于识别不同饮酒模式的效用（即，轻度、中度或重度），并鉴定其与其他生物标志物的关系和/或可与其他生物标志物一起使用以鉴定酒精使用的特定临床显著模式（目的3）。这些研究是推进磷脂酰乙醇作为酒精使用生物标志物的使用，以及确定其相对于其他生物标志物的作用以确定“真实的世界”中的饮酒模式的至关重要的一步。