Metabolism of [14C]Paracetamol and its Interactions with Aspirin in Hamsters

Abstract

1. The metabolism of [¹⁴C]paracetamol (150 mg/kg) and its interactions with aspirin (200 mg/kg) were studied in male hamsters. 2. Aspirin was found to slow the rate of paracetamol absorption from the gastro-intestinal tract, but did not affect the rate of elimination. 3. Metabolism studies showed that >80% of the radioactivity was excreted in the urine in 24 h. Paper chromatography of the urine separated the radioactivity into five peaks, four of which were identified as paracetamol and its glucuronide, sulphate and mercapturate conjugates. 4. The other peak, comprising of < 10% of the total radioactivity, was a mixture of two or more other metabolites. A major component was isolated and characterized as methyl 2-hydroxy-5-acetamidophenyl sulphone. 5. Aspirin inhibited the metabolism of paracetamol by the sulphate conjugation pathway.