Paracetamol metabolism in man

The absorption, metabolism and elimination of paracetamol was investigated in healthy subjects after therapeutic doses and also in patients with paracetamol overdosage, some of whom developed liver damage. Paracetamol disposition was also studied in relation to treatment with N-acetylcysteine (NAG),cysteamine and methionine, which were used to prevent paracetamol hepatotoxicity. Sensitive, specific and reproducible analytical methods were developed for the estimation of paracetamol and its sulphate, glucuronide, mercaoturic acid and cysteine conjugates in plasma and urine. These methods, which employed high-performance liquid chromatography, were significant improvements on existing procedures, especially in terms of simplicity and total assay times. N Following a therapeutic dose, absorption and metabolism of paracetamol was rapid and essentially complete. Paracetamol metabolism showed wide but reproducible individual variation. NAC had little appreciable effect on paracetamol elimination after a therapeutic dose but may have delayed absorption. The renal clearance of paracetamol was very low, indicating extensive renal tubular reabsorption whereas that of the sulphate and glucuronide conjugates was high, suggesting active tubular secretion. The mercapturic acid and cysteine conjugates were probably also actively secreted since they were not measureable (