What is the role of a drug-clearance test in the workup of Gilbert syndrome?

Updated: May 21, 2019
  • Author: Hisham Nazer, MBBCh, FRCP, DTM&H; Chief Editor: BS Anand, MD  more...
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In approximately 30% of patients with unconjugated hyperbilirubinemia, there is impaired clearance of bromosulfophthalein, indocyanine green, and free fatty acid, suggesting an abnormality in hepatic uptake, transport, or both. Metabolic clearance of tolbutamide is also reduced in persons with Gilbert syndrome, but because the drug does not undergo glucuronidation, hepatic uptake appears to be defective.

Plasma clearance of most drugs that undergo glucuronidation (eg, benzodiazepines) is unaffected. With regard to acetaminophen, however, patients with Gilbert syndrome are a heterogeneous group, with some demonstrating normal metabolism and others exhibiting marked reduction in glucuronidation and an increase in oxidation. [65, 66] These changes suggest that people in this subgroup may be more susceptible to liver injury after an acetaminophen overdose, though no such adverse events have been reported.

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