PHARMACOKINETICS AND PHARMACOLOGICAL EFFECTS OF ALCOHOL AFTER BARIATRIC SURGERY

描述(申请人提供)：今天，数以百万计的美国人已经做了减肥手术，考虑到肥胖流行的规模，预计这个数字将继续上升。尽管这些手术对健康有很多好处，但人们越来越担心胃旁路手术后出现的酒精问题。我们认为，上胃肠道分流引起的解剖和生理变化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旁路手术与术后酒精滥用相关的重要机制。目前的提案将是第一项研究，将使用经过验证的方法并控制体重变化的重要混杂效应，调查胃旁路手术对酒精和酒精药代动力学的主观反应的影响。将接受胃旁路手术的患者和一组接受胃捆绑手术的患者在手术前和术后9个月分别进行3次和9次相同的评估。与胃旁路手术不同的是，胃环扎术后肠/胃的解剖结构是完整的。因此，胃束带受试者将能够控制可能由减肥引起的酒精代谢和情绪影响的变化。在饮用一定剂量的酒精(0.8g或1.4g/L全身水)或非酒精安慰剂对照组之前和之后的不同时间采集呼吸和血液样本。血液酒精浓度(BAC)将通过顶空气相色谱金标准技术进行测定，并将这些浓度与从呼气样本估计的BAC进行比较。酒精影响的主观评级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 胃旁路手术和胃束带手术对酒精动力学和药效学的影响，有助于为接受这些手术的患者量身定制咨询，防止术后酒精滥用。

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.