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Abstract
1. Within 8 h after i.v. administration of paracetamol (100 mg/kg) to rats, 28.7% was excreted into bile; 1.2% dose as unchanged drug, 14.3% as the glucuronide, 8.2% as the sulphate, 4.7% as the glutathione conjugate, 0.32% as the mercapturate.
2. Rats with cannulated bile-ducts excreted 62.8% dose in the urine in 8 h compared with 83.5% in sham-operated rats. Metabolites in urine were paracetamol sulphate (63.2%), the glucuronide (12.1%), unchanged paracetamol (7%), and the mercapturate (1.2%).
3. Bile containing paracetamol and its conjugates was infused into the duodenum and within 8 h 45.3% was excreted (5.6% in bile and 39.7% in urine).
4. In rats not subjected to surgery, 91.3% dose (100 mg/kg, i.v.) was excreted in urine in 24 h. However, in rats treated twice with activated charcoal or cholestyramine (2 × 1 g/kg orally), urine excretion was decreased to 72.8 and 59.3% dose, respectively.
5. These results indicate the enterohepatic circulation of paracetamol and its metabolites in the rat.