Clinical Pharmacology & Therapeutics · 2015 · 221 citations · 50 references
MedicinePharmacologyPharmacotherapyClinical PharmacologyPharmacogeneticsPharmacogenomicsClinical Implementation Of PharmacogeneticsClinical Implementation Of PharmacogenomicsJaundice ManagementPharmacogenetic TestingPharmacokinetics In Liver DiseasePopulation PharmacogeneticsAtazanavir PharmacogeneticsGain-of-function AllelesIndirect HyperbilirubinemiaLoss-of-function AllelesReduced Function AllelesUgt1a1 GenotypeUgt1a1 GenotypingUgt1a1 Pharmacogenetics
The antiretroviral protease inhibitor atazanavir inhibits hepatic uridine diphosphate glucuronosyltransferase (UGT) 1A1, thereby preventing the glucuronidation and elimination of bilirubin. Resultant indirect hyperbilirubinemia with jaundice can cause premature discontinuation of atazanavir. Risk for bilirubin-related discontinuation is highest among individuals who carry two UGT1A1 decreased function alleles (UGT1A1*28 or *37). We summarize published literature that supports this association and provide recommendations for atazanavir prescribing when UGT1A1 genotype is known (updates at www.pharmgkb.org).
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Ernest Beutler, Terri Gelbart, Anna Demina · Proceedings of the National Academy of Sciences · 1998 · 852 citations · Full text
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