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量对血液中对乙酰氨基酚的清除和对尿对乙酰氨基酚代谢物比率的影响。这项研究的理论基础是已知的正常对乙酰氨基酚降解的定性和定量途径，以及证据表明它是氧化的次要代谢物，如果不与谷胱甘肽结合，对肝脏和肾脏都是有毒的。众所周知，禁食会导致谷胱甘肽的耗尽，在较小的程度上，还会导致葡萄糖醛酸的耗尽。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。这项研究建议在两组人中限制饮食摄入量，一组为2周内每天1,000千卡，另一组为5天，每天1至500千卡。将使用2克剂量的对乙酰氨基酚作为探针。预计血液中的药物清除量将会降低，尿液中的代谢产物将转向硫醇。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.