Skinner M H, Matano R, Hazle W, Blaschke T F
Veterans Administration Hospital, Palo Alto, CA 94304.
Methods Find Exp Clin Pharmacol. 1990 Sep;12(7):513-5.
The mercapturic acid conjugate of acetaminophen has been proposed as an index of the toxic intermediate of acetaminophen metabolism which is responsible for the increased incidence of liver injury in alcoholics taking the drug. Previous studies which compared alcoholics with normal patients failed to show any significant difference in mercapturic acid production. We undertook a longitudinal study in recovering alcoholics to test the hypothesis that abstinence should lead to a decrease in acetaminophen-mercapturic acid excretion. The patients were given a 1500 mg dose of acetaminophen soon after they stopped drinking then again approximately 2 weeks later. Urine was collected for 24 h and assayed for mercapturic acid conjugate. There was no significant difference in mercapturic acid excretion when the two measurements were compared. If the toxic intermediate hypothesis is correct, either the effect of alcohol is prolonged, or additional factor other than alcohol exposure may influence mercapturic acid excretion.
对乙酰氨基酚的巯基尿酸结合物已被提议作为对乙酰氨基酚代谢毒性中间体的一个指标，该中间体是导致服用该药物的酗酒者肝损伤发生率增加的原因。之前比较酗酒者和正常患者的研究未能显示出巯基尿酸生成有任何显著差异。我们对康复中的酗酒者进行了一项纵向研究，以检验禁欲应导致对乙酰氨基酚-巯基尿酸排泄减少这一假设。患者在停止饮酒后不久服用1500毫克对乙酰氨基酚剂量，然后在大约2周后再次服用。收集24小时尿液并检测巯基尿酸结合物。比较这两次测量结果时，巯基尿酸排泄没有显著差异。如果毒性中间体假说是正确的，那么要么酒精的影响会持续很长时间，要么除了接触酒精之外的其他因素可能会影响巯基尿酸的排泄。
