FOOD RESTRICTION ON ACETAMINOPHEN METABOLISM & DISPOSITION

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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.