Paracetamol metabolism in the rat: relationship to covalent binding and hepatic damage.
1. The degree of liver damage observed 48 h after administration of 14C ring-labelled paracetamol (3-23 mmol/kg) to rats was proportional to the amount of a highly reactive metabolite retained in the liver, bound covalently to hepatocellular proteins. 2. With increasing doses of paracetamol, urinary excretion of the glucuronide and sulphate conjugates reached a plateau, whereas the output of cysteine and mercapturic acid conjugates increased markedly. 3. The degree of covalent binding at 48 h was proportional to the rate of urinary elimination of these two latter conjugates in the first 24 h after dosing.
D000082:Acetaminophen / Q000378:metabolism* / Q000494:pharmacology / Q000652:urine; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005965:Glucuronates / Q000652:urine; D008099:Liver / Q000187:drug effects / Q000293:injuries / Q000378:metabolism*; D008297:Male; D051381:Rats; D013464:Sulfuric Acids / Q000652:urine; D013997:Time Factors
D005965:Glucuronates; D013464:Sulfuric Acids; D000082:Acetaminophen