Effect of poly rI:rC treatment upon the metabolism of [14C]-paracetamol in the BALB/cJ mouse

The effect of the immunomodulator, poly rI:rC, upon the in vivo metabolism of [14C]-paracetamol has been investigated in male BALB/cJ mice. In both poly rI:rC treated and control groups of mice the major part of the dose was excreted in the 0–24 hr urine and the major urinary metabolites were the glucuronic acid and sulphate conjugates. The urinary excretion of these two conjugates and of free paracetamol was not significantly altered following poly rI:rC treatment. Following enzymic hydrolysis of glucuronides and sulphates, the 3-cysteine, 3-mercapturate, 3-thiomethyl and 3-methylsulphoxide metabolites of paracetamol were all identified in the 0–24 hr urine together with very small amounts of 3-methoxy paracetamol. Although poly rI:rC treatment reduced the proportional urinary excretion of each of the thio adducts the individual differences were not significant. However, total thio adduct excretion, an indirect estimate of the metabolic activation of paracetamol, was significantly lower following poly rI:rC treatment. This depression in the urinary excretion of thio adducts following poly rI:rC treatment is discussed in relation to possible implications for paracetamol toxicity.