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Paracetamol metabolism in two ethnically different Spanish populations

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Summary

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.

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References

  1. Thomson J.S., Prescott L.F. (1966): Liver damage and impaired glucose tolerance after paracetamol overdose. BMJ, 2, 506–507.

    Article  PubMed  CAS  Google Scholar 

  2. Mitchell J.R., Thorgeirsson S.S., Potter W.Z., Jollow D.J., Keiser H. (1974): Acetaminophen-induced hepatic injury: protective role of glutathione in man and rationale for therapy. Clin. Pharmacol. Ther., 16, 676–684.

    PubMed  CAS  Google Scholar 

  3. Prescott L.F. (1987): Environmental modulation of paracetamol toxicity. In: Plaa G.L., Du Souich P., Erill S., Eds. Interactions between Drugs and Chemicals in Industrial Societies. Esteve Foundation Symposia, vol 2, Amsterdam: Elsevier, 161–174.

    Google Scholar 

  4. Mucklow J.C., Fraser H.S., Bulpitt J., Kahn C., Mould G., Dollery C.T. (1980): Environmental factors affecting paracetamol metabolism in London factory and office workers. Br. J. Clin. Pharmacol., 10, 67–74.

    PubMed  CAS  Google Scholar 

  5. Nash R.M., Stein L., Penno M.B., Passananti G.T., Vesell E.S. (1984): Sources of interindividual variations in acetaminophen and antipyrine metabolism. Clin. Pharmacol. Ther., 36, 417–430.

    PubMed  CAS  Google Scholar 

  6. Kalow W. (1982): Ethnic differences in drug metabolism. Clin. Pharmacokinet., 7, 373–400.

    Article  PubMed  CAS  Google Scholar 

  7. Clements J.A., Critchley J.A.J.H., Prescott L.F. (1984): The role of sulphate conjugation in the metabolism and disposition of oral and intravenous paracetamol in man. Br. J. Clin. Pharmacol., 18, 481–485.

    PubMed  CAS  Google Scholar 

  8. Critchley J.A.J.H., Nimmo G.R., Gregson C.A., Woolhouse N.M., Prescott L.F. (1986): Inter-subject and ethnic differences in paracetamol metabolism. Br. J. Clin. Pharmacol., 22, 649–657.

    PubMed  CAS  Google Scholar 

  9. Esteban A., Graells M., Satorre J., Pérez-Mateo M. (1992): Determination of paracetamol and its four major metabolites in mouse plasma by reversed-phase ion-pair high-performance liquid chromatography. J. Chromatogr., 573, 121–126.

    Article  PubMed  CAS  Google Scholar 

  10. Lee H.S., Ti T.Y., Koh Y.K., Prescott L.F. (1992): Paracetamol elimination in Chinese and Indians in Singapore. Eur. J. Clin. Pharmacol., 43, 81–84.

    Article  PubMed  CAS  Google Scholar 

  11. Patel M., Tang B.K., Kalow W. (1992): Variability of acetaminophen metabolism in Caucasians and orientals. Pharmacogenetics, 2, 38–45.

    Article  PubMed  CAS  Google Scholar 

  12. Aguirre A., Vicario A., Mazón L.I. et al. (1991): Are the Basques a single and unique population? Am. J. Hum. Genet., 49, 450–458.

    PubMed  CAS  Google Scholar 

  13. Ladds G., Wilson K., Burnett D. (1987): Automated liquid chromatographic method for the determination of paracetamol and six metabolites in human urine. J. Chromatogr., 414, 355–364.

    Article  PubMed  CAS  Google Scholar 

  14. Prescott L.F. (1983): Paracetamol overdosage. Pharmacological considerations and clinical management. Drugs, 25, 290–314.

    Article  PubMed  CAS  Google Scholar 

  15. Critchley J.A.J.H., Dyson E.H., Scott A.W., Jarvie D.R., Prescott L.F. (1983): Is there a place for cimetidine or ethanol in the treatment of paracetamol poisoning? Lancet, 1, 1375–1376.

    Article  PubMed  CAS  Google Scholar 

  16. Miners J.O., Attwood J., Birkett D.J. (1983): Influence of sex and oral contraceptive steroids on paracetamol metabolism. Br. J. Clin. Pharmacol., 16, 503–509.

    PubMed  CAS  Google Scholar 

  17. De Morais S.M.F., Uetrecht J.P., Wells P.G. (1992): Decreased glucuronidation and increased bioactivation of acetaminophen in Gilbert’s syndrome. Gastroenterology, 102, 577–586.

    PubMed  Google Scholar 

  18. Esteban A., Pérez-Mateo M. (1993): Gilbert’s disease: a risk factor for paracetamol overdosage? J. Hepatol., 18, 257–258.

    Article  PubMed  CAS  Google Scholar 

  19. Miners J.O., Attwood J., Birkett D.J. (1984): Determinants of acetaminophen metabolism: effect of inducers and inhibitors of drug metabolism on acetaminophen’s metabolic pathways. Clin. Pharmacol. Ther., 35, 480–486.

    PubMed  CAS  Google Scholar 

  20. Bock K.W., Wiltfang J., Blume R., Ullrich D., Bircher J. (1987): Paracetamol as a test drug to determine glucuronide formation in man. Effects of inducers and of smoking. Eur. J. Clin. Pharmacol., 31, 677–683.

    Article  PubMed  CAS  Google Scholar 

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Esteban, A., Calvo, R. & Pérez-Mateo, M. Paracetamol metabolism in two ethnically different Spanish populations. European Journal of Drug Metabolism and Pharmacokinetics 21, 233–239 (1996). https://doi.org/10.1007/BF03189719

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