Paracetamol metabolism in two ethnically different Spanish populations

The 24 h urinary excretion of paracetamol and its metabolites following a single oral dose of 1.5 g was compared in two ethnically different Spanish populations: 39 volunteers from the Basque country and 32 from Alicante. The urinary concentrations of unchanged paracetamol and its glucuronide, sulphate, cysteine, and mercapturic acid conjugates were determined by high-performance liquid chromatography. Statistically significant differences in the urinary excretion of unchanged paracetamol and the fractional urinary recovery of each conjugate between subjects from Alicante and subjects from the Basque country were not found. In both populations, an inverse relationship between glucuronide and sulphate conjugation following a bimodal frequency distribution pattern was found. In contrast to paracetamol oxidation, intersubject variation in paracetamol conjugation was negligible. ?The urinary excretion of unchanged paracetamol was higher in smokers than in nonsmokers. As compared with other studies, the urinary excretion of oxidation-derived paracetamol metabolites in both Spanish populations was intermediate and significantly different than that found in Caucasians from Scotland and West Africans (Ghana). This may determine a susceptibility to paracetamol hepatotoxicity following overdosage in the Spanish population.