Related Experiment Video
Updated: Sep 29, 2026

Mass Spectrometry and Luminogenic-based Approaches to Characterize Phase I Metabolic Competency of In Vitro Cell Cultures
Published on: March 28, 2017
[The heterogeneity of paracetamol metabolism in Gilbert's disease]
A Esteban Rodríguez1, M Pérez-Mateo Regadera
1Unidad de Investigación, Hospital General Universitario de Elche.
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.
Material And 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.
Related Concept Videos
Pharmacokinetics in Pediatric Patients: Drug Metabolism
Effect of Hepatic Disease on Pharmacokinetics: Drug Dosing and Hepatic Blood Flow
Effect of Hepatic Disease on Pharmacokinetics: Pathophysiologic Assessment and Liver Function Test
Pharmacogenetics of Drug Metabolism: Overview
Pharmacogenetics of Phase I Enzymes: Cytochrome P450 Isozymes
Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase

