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消除和尿液中对乙酰氨基酚代谢物比例的影响。 本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，以及其是氧化性次要代谢产物的证据，如果不与谷胱甘肽结合，则对肝脏具有毒性，其次对肾脏具有毒性。 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。 该研究建议限制两组的饮食摄入量，一组为1,000千卡/天，持续2周，另一组为500千卡/天，持续5天。 将使用2 gm剂量的对乙酰氨基酚作为探针。 预计药物从血液中的清除率将降低，尿代谢物将向硫醇转移。 这将与血浆谷胱甘肽相关，因为其中60%来自肝脏。

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.