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.
Similar content being viewed by others
References
Thomson J.S., Prescott L.F. (1966): Liver damage and impaired glucose tolerance after paracetamol overdose. BMJ, 2, 506–507.
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.
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.
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.
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.
Kalow W. (1982): Ethnic differences in drug metabolism. Clin. Pharmacokinet., 7, 373–400.
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.
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.
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.
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.
Patel M., Tang B.K., Kalow W. (1992): Variability of acetaminophen metabolism in Caucasians and orientals. Pharmacogenetics, 2, 38–45.
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.
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.
Prescott L.F. (1983): Paracetamol overdosage. Pharmacological considerations and clinical management. Drugs, 25, 290–314.
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.
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.
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.
Esteban A., Pérez-Mateo M. (1993): Gilbert’s disease: a risk factor for paracetamol overdosage? J. Hepatol., 18, 257–258.
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.
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.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
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
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF03189719