Effect of aspirin on fate of ¹⁴C-acetaminophen in guinea pigs

The interaction of ¹⁴C-acetaminophen, 150 mg/kg (20 μCi/kg), and orally administered aspirin, 200 mg/kg, was studied in male guinea pigs. Aspirin-pretreated animals possessed higher ¹⁴C blood levels than controls. Paper chromatography of 0–6-hr urines demonstrated that pretreated animals excreted significantly greater amounts of mercapturate than controls; however, it was only a minor metabolite, accounting for 1–3% of the counts in the urine. The major metabolite, the glucuronide, accounted for 90% of the counts, with free acetaminophen and its sulfate responsible for the remaining counts. Tissue distribution studies indicated that blood plasma and kidneys from aspirin-pretreated animals possessed statistically higher ¹⁴C levels than did control tissues. Bile duct and ureter cannulation experiments indicated that aspirin inhibited the concentrating processes into the urine and bile.