[The heterogeneity of paracetamol metabolism in Gilbert's disease].
BACKGROUND
Gilbert's syndrome (GS) is a hereditary deficiency of bilirubin UDP-glucuronosyltransferase (UGT). The aim of this study was to analyze changes in the metabolism of paracetamol, which is primarily eliminated by liver glucuronidation, through urine concentrations of its four principal hepatic metabolites, in persons with GS.


METHODS
Thirty-two healthy volunteers and 18 persons with GS were studied. Subjects were given 1.5 g of oral paracetamol. Elimination of free paracetamol, as well as derivatives of its conjugation (glucuronide, sulfate) and of its oxidation (cysteine, mercapturic acid), was determined in 24-hour urine by high performance liquid chromatography (HPLC). Results were expressed as a percentage of the total quantity of paracetamol eliminated. Patients with GS were divided in two subgroups (GS-I and GS-II) according to whether glucuronidation was greater than or less than 50%.


RESULTS
Patients with GS showed no significant differences in the urinary elimination of metabolites compared with controls. However, the subgroup GS-II showed decreased glucuronidation (p = 0.0012) and increased oxidation (p = 0.0051) compared with the other two groups. Moreover, there was an inverse correlation between the glucuronide conjugate and oxidation derivatives (r = 0.08718; p < 0.005).


CONCLUSIONS
Persons with GS form a heterogeneous group as far as paracetamol metabolism is concerned. In one subgroup metabolism was normal and in the other glucuronication was clearly decreased and oxidation was increased. These alterations could make these subjects more susceptible to liver damage after paracetamol overdose.
Unidad de Investigación, Hospital General Universitario de Elche.
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Esteban Rodríguez
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Pérez-Mateo Regadera
D000082:Acetaminophen / Q000493:pharmacokinetics* / Q000652:urine; D000328:Adult; D018712:Analgesics, Non-Narcotic / Q000493:pharmacokinetics* / Q000652:urine; D016009:Chi-Square Distribution; D005260:Female; D005878:Gilbert Disease / Q000652:urine*; D006801:Humans; D008297:Male; D010084:Oxidation-Reduction; D018709:Statistics, Nonparametric
D018712:Analgesics, Non-Narcotic; D000082:Acetaminophen
Heterogeneidad del metabolismo del paracetamol en la enfermedad de Gilbert.