PHARMACOKINETICS AND PHARMACOLOGICAL EFFECTS OF ALCOHOL AFTER BARIATRIC SURGERY

描述（由申请人提供）：今天，数以百万计的美国人进行了减肥手术，鉴于肥胖流行病的严重性，预计这一数字将继续上升。尽管这些手术对健康有很多好处，但人们越来越关注胃旁路手术后酒精问题的发展。我们认为，由于上胃肠道改道引起的解剖和生理变化而导致的酒精药代动力学和对酒精的主观反应的变化可能是胃分流术与术后酒精滥用之间关联的重要机制。目前的建议将是第一个研究胃旁路手术对酒精和酒精药代动力学的主观反应的影响，使用经过验证的方法，并控制体重变化的重要混杂效应。胃分流术患者和胃束带术患者术前评估3次，术后9 m评估3次，手术程序相同。与胃旁路手术不同，胃束带手术后肠/胃的解剖结构是完整的。因此，胃束带可以控制体重减轻可能引起的酒精代谢和情绪影响的变化。呼吸和血液样本将在摄入一定量的酒精（0.8或1.4 g/l的全身水分）或非酒精安慰剂对照之前和之后的不同时间被采集。血液酒精浓度（BAC）将由顶空气相色谱金标准技术测定，这些浓度将与呼吸样本估计的BAC进行比较。酒精影响的主观评分将通过在该领域广泛使用的有效问卷来衡量。我们的研究结果将为理解奠定基础

DESCRIPTION (provided by applicant): Today, millions of Americans have had bariatric surgery, and given the magnitude of the obesity epidemic, it is anticipated that this number will continue to rise. Despite the numerous health benefits of these procedures, there is a growing concern with the development of alcohol problems after gastric bypass surgery. We believe that changes in alcohol pharmacokinetics and subjective responses to alcohol that occur as a result of the anatomical and physiological changes caused by upper gastrointestinal tract diversion might be an important mechanism responsible for the association between gastric bypass surgery and postoperative alcohol abuse. The current proposal will be the first study that will investigate the effects of gastric bypass surgery on subjective responses to alcohol and alcohol pharmacokinetic using validated methods and controlling for the important confounding effect of changes in body weight. Patients who will undergo gastric bypass surgery and a group of patients undergoing banding gastric surgery will be evaluated 3 times before and 3 times 9 m after surgery following identical procedures. Unlike after gastric bypass, the anatomy of the intestine/stomach is intact after gastric banding. Thus, gastric banding subjects will allow controlling for changes in alcohol metabolism and mood effects that could be caused by weight loss. Breath and blood samples will be taken before and at various times after a dose of alcohol (0.8 or 1.4 g/l of total body water) or non-alcoholic placebo control are consumed. Blood alcohol concentrations (BAC) will be determined by the gold standard technique of headspace gas chromatography and these concentrations will be compared with the BAC estimated from breath samples. Subjective ratings of alcohol effects will be measured by validated questionnaires extensively used in the field. The results from our study will lay the foundation for understanding the effect of gastric bypass and gastric banding procedures on alcohol kinetics and pharmacodynamics, which can help tailor counseling in patients undergoing these procedures and prevent alcohol misuse after surgery.