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Abstract
1. Metabolism of aspirin was studied in 10 human volunteers who took a therapeutic dose (600 mg) by mouth and in nine patients who took aspirin in overdose.
2. Salicyluric acid was the major urinary metabolite in volunteers (63.1 ± 8.4% of dose in 0-8 h). In overdose patients, salicyluric acid in urine was decreased (30.0 ± 8.2%, 0-24 h, P<0.001) and there was increased elimination of salicylic acid (34.1%, P<0.005), salicyl acyl glucuronide (14.4%, P<0.05) and gentisuric acid (5.3%).
3. Metabolism of orally administered 14C-aspirin in rats over a 10-fold dose range (10-100 mg/kg) resulted in excretion of 81-91% dose in urine in the first 24 h. Salicylic acid was the major urinary metabolite (43-51% dose). Excretion of salicyluric acid decreased with increasing dose, whereas gentisic acid and salicyl phenolic and acyl glucuronides increased.
4. The profile of aspirin metabolites was qualitatively similar in man and rat but there were quantitative differences. Limited capacity to form salicyluric acid was observed in both species. Dependence on this pathway in rat was low and was compensated by increased utilization of other routes; dependence on salicyluric acid formation in man was high and in overdose, compensation by other routes was incomplete.
