Gilbert's syndrome is associated with a mutation in the gene which encodes for the enzyme, uridine diphosphate glucuronosyltransferase (UGT) 1A1. Individuals with Gilbert's syndrome have reduced levels of UGT 1A1 and may be predisposed to adverse reactions from drugs metabolised by UGT 1A1.
Gilbert's syndrome is generally a benign condition that is present in up to 10% of the population.
Irinotecan and its active metabolite, SN-38, are glucuronidated by UGT 1A1 to inactive compounds. Individuals with Gilbert's syndrome are at risk of increased toxicity due to irinotecan or sacituzumab govitecan (an antibody-drug conjugate linked to SN-38).