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".
Excessive alcohol consumption is the third-leading preventable cause of death in the United States. The proposed study will identify the clinical utility of a promising new alcohol biomarker, make direct comparisons with other established biomarkers, and determine how they may be collectively used to better identify problematic drinking. The results of this study lay the foundation for future work identifying the appropriate application of alcohol-use biomarkers in prevention and treatment programs.