Pharmacogenetic testing for uridine diphosphate glucuronosyltransferase 1A1 polymorphisms: are we there yet?
Recent changes to the labels of three prescription drugs--irinotecan, 6-mercaptopurine, and warfarin--include recommendations for pharmacogenetic testing in patients. Thus, clinicians are faced with determining the utility and practicality of pharmacogenetic testing in clinical practice. We illustrate the clinical implications that this testing may have using irinotecan, an agent approved for the treatment of metastatic colorectal cancer, as an example. A clinical association between the drug's active metabolite and toxicity has been found. By performing uridine diphosphate glucuronosyltransferase (UGT) 1A1 genetic testing, some studies have been able to predict which patients receiving irinotecan will experience the toxicity. Thus, irinotecan's package insert was revised to include a recommendation for such testing. In addition, the United States Food and Drug Administration approved a clinical test for the UGT1A1*28 allele. These events demonstrate that pharmacogenetics has entered the realm of clinical practice. However, the transition from bench to bedside of these tests has distinct challenges such as population differences, test sensitivity, and the role of other genetic and nongenetic factors that influence drug toxicity. In addition, ethical and logistic implications of pharmacogenetic testing exist.
Perera
Minoli A
MA
Sections of Genetic Medicine, Department of Medicine, University of Chicago, Chicago, Illinois, USA.
Innocenti
Federico
F
Ratain
Mark J
MJ
D002166:Camptothecin / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D000077146:Irinotecan; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D011480:Protease Inhibitors / Q000494:pharmacology; D000099148:UGT1A1 Enzyme
D002166:Camptothecin; D014453:Glucuronosyltransferase; D000077146:Irinotecan; D011480:Protease Inhibitors; D000099148:UGT1A1 Enzyme