The metabolism of paracetamol has been studied in man following a therapeutic dose, in neonates who received the drug via breast milk, in patients with rheumatoid arthritis and hyperthyroidism, in the presence of salicylamide and after overdose. The finding of acid-labile prearomatic species in urine has led to the suggestion that these metabolites might arise from an epoxide. The metabolism of aspirin in man was investigated in normal volunteers after a therapeutic dose, in patients with rheumatoid arthritis and after overdose. An age effect was noted in the metabolism of paracetamol and aspirin in normal volunteers. The urinary metabolic profile of both paracetamol and aspirin in rheumotoid patients was different from that of normal volunteers. Recoveries of paracetamol and its metabolites in neonatal urine was different from normal volunteers. Predosing with salicylamide affected both the AUC and the urinary metabolic profile of paracetamol. Administration of L-methionine and/or N-acetyl cysteine to paracetamol poisoned patients appeared to replete both sulphate and glutathione stores. Aspirin overdosed patients showed a lower recovery of salicyluric acid in urine than normals. The metabolism of paracetamol in mice and guinea pigs has been investigated in single and repeated doses in the presence of enzyme inducing agents and metabolic competing agents. The metabolism of paracetamol in the presence of L-methionine in rabbits has also been studied. Pretreatment with inducing agents, concurrent treatment with competing agents and repeated dosing were found to alter the metabolism of paracetamol when compared with a single dose of paracetamol alone. A large dose of paracetamol administered to rabbits showed a different metabolic profile from a small dose of paracetamol and from the large dose given concurrently with L-methionine.
|Date of Award||1983|