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Pharmacogenetic testing for uridine diphosphate glucuronosyltransferase 1A1 polymorphisms: are we there yet?
Minoli A Perera1, Federico Innocenti, Mark J Ratain
1Sections of Genetic Medicine, Department of Medicine, University of Chicago, Chicago, Illinois, USA.
Pharmacotherapy
|May 28, 2008
Summary
Pharmacogenetic testing, like uridine diphosphate glucuronosyltransferase (UGT) 1A1 genetic testing for irinotecan, is now in clinical practice. Challenges remain in implementing these tests due to various factors.
Area of Science:
- Pharmacogenomics
- Clinical Pharmacology
- Genetics
Background:
- Recent prescription drug label changes for irinotecan, 6-mercaptopurine, and warfarin recommend pharmacogenetic testing.
- Clinicians face challenges in integrating pharmacogenetic testing into routine practice.
Purpose of the Study:
- To illustrate the clinical implications of pharmacogenetic testing using irinotecan as an example.
- To highlight the transition of pharmacogenetics from research to clinical application.
Main Methods:
- Review of clinical associations between drug metabolites and toxicity.
- Analysis of uridine diphosphate glucuronosyltransferase (UGT) 1A1 genetic testing for irinotecan toxicity prediction.
- Examination of FDA approval of UGT1A1*28 allele testing.
Main Results:
- A clinical association between irinotecan's active metabolite and toxicity has been identified.
- UGT1A1 genetic testing can predict irinotecan-induced toxicity in some patients.
- Irinotecan labeling was updated to recommend UGT1A1 testing; a UGT1A1*28 allele test was FDA-approved.
Conclusions:
- Pharmacogenetics has entered clinical practice, exemplified by irinotecan.
- Challenges such as population variability, test sensitivity, and multifactorial drug toxicity must be addressed.
- Ethical and logistical considerations are crucial for the successful implementation of pharmacogenetic testing.
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