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CHAPTER 5 Pharmacogenomics 87

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C ASE STUD Y ANSWER

Atazanavir inhibits the polymorphic UGT1A1 enzyme, and at least 5 times the upper limit of normal (grade 4 eleva-
which mediates the conjugation of glucuronic acid with tion) in approximately 4.8% of patients. Carriers of the
bilirubin. Decreased UGT1A1 activity results in the accu- UGT1A1 decreased function alleles (*28/*28 or *28/*37)
mulation of unconjugated (indirect) bilirubin in blood and have reduced enzyme activity and have an increased risk
tissues. When levels are high enough, yellow discoloration of atazanavir discontinuation. Genotyping showed that the
of the eyes and skin, ie, jaundice, is the result. The plasma patient was homozygous for the UGT1A1*28 allele polymor-
levels of indirect bilirubin concentrations are expected to phism. This probably led to the high levels of bilirubin and
increase to greater than 2.5 times the upper limit of nor- the subsequent discontinuation of atazanavir secondary to
mal (grade 3 or higher elevations) in approximately 40% of the adverse drug reaction of jaundice.
patients taking once-daily atazanavir boosted with ritonavir