Villeneuve J P, Raymond G, Bruneau J, Colpron L, Pomier-Layrargues G
Gastroenterol Clin Biol. 1983 Nov;7(11):898-902.
It is well known that a chemically reactive metabolite of acetaminophen formed in the liver can cause hepatic necrosis. The amount of cysteine and N-acetylcysteine derivatives excreted in the urine is an index of the amount of reactive metabolite produced. We have examined the pharmacokinetics and the pattern of acetaminophen metabolites in the urine, in 6 healthy controls, in 9 alcoholic subjects without liver disease, and in 11 patients with alcoholic cirrhosis but abstaining from alcohol. In alcoholics, oral clearance of the drug was similar to that of control subjects, but the amount of cysteine and N-acetylcysteine conjugates excreted in urine was significantly increased. In cirrhotics, the clearance of acetaminophen was decreased by 50 p. 100, but the pattern of urinary metabolites was unchanged. These results support previous anecdotal reports of increased acetaminophen hepatotoxicity in alcoholic subjects.
众所周知，对乙酰氨基酚在肝脏中形成的化学反应性代谢产物可导致肝坏死。尿液中排泄的半胱氨酸和N - 乙酰半胱氨酸衍生物的量是所产生的反应性代谢产物量的一个指标。我们已经研究了6名健康对照者、9名无肝脏疾病的酗酒者以及11名戒酒的酒精性肝硬化患者中对乙酰氨基酚的药代动力学和尿液中代谢产物的模式。在酗酒者中，该药物的口服清除率与对照受试者相似，但尿液中排泄的半胱氨酸和N - 乙酰半胱氨酸结合物的量显著增加。在肝硬化患者中，对乙酰氨基酚的清除率降低了50%，但尿液代谢产物的模式没有改变。这些结果支持了先前关于酗酒者中对乙酰氨基酚肝毒性增加的传闻报道。
