Ethanol metabolites for monitoring drinking in clinical trials.

描述（由申请人提供）：识别近期饮酒是关注酒精使用障碍的临床试验和治疗计划的关键组成部分。与其他药物滥用治疗计划不同，其中尿液药物筛查提供了最近药物使用的客观证据，窗口期为几天，酒精重点计划通常必须依赖于自我报告。乙基葡萄糖醛酸苷（EtG）和硫酸乙酯（EtS）是乙醇的次要代谢产物，是近期酒精摄入的高度特异性和敏感性指标，并且可以在生物液体中测量的时间比乙醇本身长得多。因此，他们有希望作为监测最近的乙醇使用或相反，记录在治疗试验和治疗计划禁欲急需的客观标志物。与法医学或流行病学相比，它们在治疗环境中的应用尚未在对照的、有充分记录的临床试验中得到充分研究。我们将在两项NIAAA资助的门诊临床试验的背景下进行乙醇挑战研究并研究EtG/EtS，以满足以下特定目标：目的1：我们将表征尿液EtG和EtS消除，包括受试者间和受试者内变异性以及选择一系列乙醇剂量后的剂量依赖性，以产生轻度至重度饮酒后预期的血液酒精浓度。目标2：我们将在规定的时间间隔内确定参与以禁欲为目标的临床试验和AIM 3：以适度为目标的单独临床试验的受试者中EtG和EtS的浓度和浓度变化。在这两种情况下，我们将这些措施与更传统的结果措施，包括自我报告，血液酒精浓度，碳水化合物缺乏转铁蛋白和γ谷氨酰转移酶。这些研究应该为酒精使用障碍的研究和管理中最佳使用这些有前途的新标志物提供指导。 公共卫生相关性：需要一个客观的标记和测量最近的饮酒量的最佳调查的治疗方案和管理的患者在临床试验和治疗方案。我们拟定的研究应确定测量次要乙醇代谢产物乙基葡萄糖醛酸苷和硫酸乙酯的效用，以及新治疗方法的研究，并为在酒精使用障碍治疗中适当使用这些标志物提供指导。

DESCRIPTION (provided by applicant): Identification of recent alcohol consumption is a critical component of clinical trials and treatment programs that focus on alcohol use disorders. Unlike other substance abuse treatment programs, wherein urine drug screening provides objective evidence of recent drug use with a window of several days, alcohol focused programs must usually depend on self reports for this information. Ethyl glucuronide (EtG), and ethyl sulfate (EtS), minor metabolites of ethanol, are highly specific and sensitive indicators of recent alcohol ingestion, and can be measured in biological fluids for considerably longer than ethanol itself. Thus, they have promise as much needed objective markers for monitoring recent ethanol use or conversely, documenting abstinence in therapeutic trials and treatment programs. Their application in the therapeutic setting, in contrast to the forensic or epidemiological, has not yet been sufficiently investigated in the context of controlled, well documented clinical trials. We will conduct an ethanol challenge study and investigate EtG/EtS in the context of two NIAAA funded outpatient clinical trials in order to meet the following Specific Aims: AIM 1: We will characterize urinary EtG and EtS elimination, including inter-subject and intrasubject variability and dose dependency following a range of ethanol doses selected to produce blood alcohol concentrations that would be expected following light to heavy drinking. AIM 2: We will determine concentrations and changes in concentration of EtG and EtS at defined intervals in subjects participating in a clinical trial that has a goal of abstinence and AIM 3: in a separate clinical trial that has a goal of moderation. In both, we will correlate these measures with more traditional outcome measures, including self reports, blood alcohol concentrations, carbohydrate deficient transferrin and gamma glutamyl transferase. These studies should provide guidelines for optimal use of these promising new markers in the study and management of alcohol use disorders. PUBLIC HEALTH RELEVANCE: An objective marker and measure of recent alcohol consumption is needed for the optimal investigation of treatment options and for the management of patients in clinical trials and treatment programs respectively. Our proposed studies should define the utility of measuring the minor ethanol metabolites, ethyl glucuronide and ethyl sulfate, in conjunction with the study of new treatments, and also yield guidelines for appropriate use of these markers in the treatment of alcohol use disorders.