• Aspirin is extensively hydrolyzed to salicylic acid during absorption after oral administration. This hydrolysis is completed systemically. Salicylic acid, an effective analgesic, antipyretic, and antiinflammatory agent, is eliminated by renal excretion and by metabolic conversion to conjugates with glycine and glucuronic acid, respectively, and to gentisic acid. Two of these metabolic processes are easily saturable, causing systemic clearance of salicylate to decrease with increasing dose. Acetaminophen metabolism during absorption is minor, and the drug is eliminated primarily by conjugation with glucuronic acid and with sulfate to pharmacologically inactive products. These processes become saturated only in the supertherapeutic dose range, thereby causing an increase in the fraction of the dose converted to a minor but potentially hepatotoxic metabolite. In the usual therapeutic dose range, acetaminophen is much more rapidly eliminated from the body than is salicylic acid.
(Arch Intern Med 1981;141:279-281)