Paracetamol metabolism in chronic liver disease

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Abstract
Summary The plasma concentrations and urinary excretion of paracetamol and its glucuronide, sulphate, cysteine and mercapturic acid conjugates were measured in eight normal subjects, eight patients with mild liver disease and seven patients with severe liver disease following an oral dose of 1.5 g of paracetamol. The mean plasma paracetamol half-life was similar in normal subjects (2.43 h±0.19) and those with mild liver disease (2.16 h±0.54) but was significantly prolonged in all patients with severe liver disease (4.25 h±1.15:p=<0.001). Prolongation of the paracetamol half-life was related to reduced plasma albumin and increased prothrombin time. The mean ratios of plasma concentrations of unchanged paracetamol to paracetamol glucuronide and sulphate were significantly greater in patients with severe liver disease than the normal subjects. There were no significant differences in the overall 24-h urinary excretion of paracetamol and its glucuronide, sulphate, cysteine and mercapturic acid conjugates in the three groups. The glutathione conjugation of paracetamol did not seem to be impaired in patients with severe liver disease as evidenced by the production of normal amounts of the cysteine and mercapturic acid conjugates. There is thus no evidence that they are at increased risk of hepatotoxicity when given a single therapeutic dose of paracetamol.