FOOD RESTRICTION ON ACETAMINOPHEN METABOLISM & DISPOSITION

本研究的目的是确定肥胖患者减少食物摄入对血液中对乙酰氨基酚的消除和尿中对乙酰氨基酚代谢物比例的影响。这项研究的理论基础是已知的对乙酰氨基酚正常降解的定性和定量途径，以及它是氧化次要代谢物的证据，如果不与谷胱甘肽结合，对肝脏有毒，其次对肾脏有毒。众所周知，禁食会导致谷胱甘肽的消耗，并在较小程度上导致葡萄糖醛酸的消耗。最终的结果将是更多的对乙酰氨基酚分流到有毒的氧化途径。该研究建议将饮食摄入量限制在两组，一组每天1000千卡，持续两周，一组每天500千卡，持续5天。2克剂量的对乙酰氨基酚将被用作探针。预计血液中的药物去除量会降低，尿代谢物会向巯基转移。这将与血浆谷胱甘肽有关，因为60%的血浆谷胱甘肽来源于肝脏。

The purpose of this study is to determine the effects of decreased food intake by obese patients on the elimination of acetaminophen from blood and on the acetaminophen metabolite ratio in urine. The theoretical basis of the study is the known qualitative and quantitative pathways of normal acetaminophen degradation and the evidence that it is the oxidative minor metabolite which, if not combined with glutathione, is toxic to the liver and, secondarily, to the kidney. It is known that fasting results in depletion of glutathione and, to a lesser extent, of glucuronic acid. The net result would be a shunting of more acetaminophen to the toxic oxidative pathway. The study proposes to restrict dietary intake in two groups, one to 1,000 kcal/day for 2 weeks and one to 500 kcal/day for 5 days. A 2 gm dose of acetaminophen will be used as a probe. It is expected that there will be lower drug removal from blood and a shift in urinary metbolites toward mercaptide. This will be correlated with plasma glutathione, as 60% of this is derived from liver.