Pharmacokinetics and metabolism of acetaminophen in normal, alcoholic and cirrhotic subjects

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.