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表征合成和消除磷脂酰乙醇在实验室环境中作为酒精使用的生物标志物的药代动力学，然后单独确定其临床实用性，并共同确定其他已建立的生物标志物。我们将使用一种创新的方法客观地表征“现实世界”中的酒精使用，并在酒精领域使用两个进步：（1）透皮酒精监测设备以及可以客观地量化酒精使用的方法的改进； （2）最近的乙醇生化代谢产物的表征称为磷脂酰乙醇，磷脂酰乙醇是一种磷脂，并储存在红细胞中。磷脂酰乙醇似乎具有独特的特征作为饮酒的生物标志物，包括更长的检测窗口（与其他直接标记相比）及其对酒精消耗的高特异性（与间接标记相比）。我们提出了三项研究来表征和验证该标记物。在研究1和2中，我们将分别在几天内分别施用酒精和一系列连续剂量的酒精后，将表征和消除磷脂酰乙醇的合成和消除。这两项研究将以光线（男性和男性每天<2饮料）和重量饮酒者（女性饮料/天饮料为e4饮料，男性为E5）进行，将使用两剂剂量的酒精（0.4或0.8 g/kg）进行。这些研究将使我们能够检查单个或多个饮酒事件后如何合成磷脂酰乙醇。在研究3中，轻度，中度（女性每天2-3杯饮料，男性2-4饮料），将招募大量饮酒者，以佩戴透皮酒精监测设备28天，并被要求照常喝酒。他们将每周访问诊所 提供血液和尿液样品，该样品将用于分析磷脂酰乙醇和其他酒精生物标志物。这项最后一项研究将使我们能够确定彼得（Peth）单独（以及与其他3种生物标志物）如何用于识别个人的水平和饮酒方式。这项研究使我们能够解决三个主要目的：在轻度和重饮料中，检查单个酒精剂量（0.4或0.8 g/kg）后，检查磷脂酰乙醇合成和消除的药代动力学（AIM 1）；在轻度和重饮酒者中，检查连续5天饮酒（0.4 g/kg）的磷脂酰乙醇合成，积累和消除的药代动力学（AIM 2）；并确定磷脂酰乙醇的效用，以鉴定自然中观察到的不同饮酒模式（即光，中度或重型），并确定与其他生物标志物之间的关系和/或可以与其他生物标志物一起使用，以识别特定临床上重要的酒精使用模式（AIM 3）。这些研究在推进使用磷脂酰乙醇作为酒精的生物标志物以及鉴定其相对于其他生物标志物来识别“现实世界”中的饮酒模式的作用方面至关重要。