Heterogeneity of paracetamol metabolism in Gilbert’s syndrome

  • A. Esteban
  • M. Pérez-Mateo

DOI: 10.1007/BF03190005

Cite this article as:
Esteban, A. & Pérez-Mateo, M. Eur. J. Drug Metab. Pharmacokinet. (1999) 24: 9. doi:10.1007/BF03190005


Gilbert’s syndrome (GS) is an inherited bilirubin UDP-glucuronosyl transferase deficiency. The object of this study was to investigate the possible effects of this disorder on the metabolism of a drug, such as paracetamol, which is basically eliminated by hepatic glucuronidation. We studied 32 healthy volunteers and 18 people with GS, all of whom were given 1.5 g of paracetamol orally. In the 24 h urine collected, we determined the elimination of free paracetamol, the conjugates (glucuronide, sulphate) and the oxidation products (cysteine, mercapturic acid) by high pressure liquid chromatography (HPLC). The results are given as a percentage of the total quantity of paracetamol eliminated. The patients with GS were divided into 2 subgroups (GS-I and GS-II) according to whether glucuronidation was more or less than 50%. The overall results of the GS group showed no significant difference in the urinary elimination of metabolites as compared to the control group. However, in subgroup GS-I, a reduction in glucuronidation (P=0.0012) and an increase in oxidation (P=0.0051) was seen, as compared with the other 2 groups. There was inverse correlation between the glucuronide produced by conjugation and the oxidation products (r=−0.8718;P<0.005). People with GS are a heterogeneous group with respect to the metabolism of paracetamol. In one subgroup this was normal. In the other subgroup there was a marked reduction in glucuronidation and an increase in oxidation. These changes could mean that people in this subgroup are more liable to liver damage after an overdose of paracetamol.


Paracetamol metabolism Gilbert’s syndrome paracetamol conjugates hepatotoxicity glucuronidation 

Copyright information

© Springer-Verlag 1999

Authors and Affiliations

  • A. Esteban
    • 1
  • M. Pérez-Mateo
    • 2
  1. 1.Research Unit, Universidad Miguel HernandezHospital General Universitario de ElcheAlicante
  2. 2.Department of Internal Medicine, Universidad Miguel HernandezHospital General Universitario de AlicanteAlicanteSpain
  3. 3.Servicio de Medicina InternaHospital General UniversitarioAlicanteSpain

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