Pharmacogenetics of irinotecan disposition and toxicity: a review
- PMID: 20406168
- DOI: 10.2174/157488410791498806
Pharmacogenetics of irinotecan disposition and toxicity: a review
Abstract
Irinotecan (CPT-11) is a widely used anticancer drug, especially for the treatment of colorectal cancer. Irinotecan is considered an inactive prodrug that requires activation to the active metabolite SN-38. Patients treated with irinotecan occasionally experience severe neutropenia and delayed diarrhea, and the occurrence of these adverse reactions is unpredictable and still largely unexplained. Various studies have demonstrated a relationship between SN-38 pharmacokinetics and the experienced toxicity. In recent years, genetic polymorphisms in UDP-glucuronosyltransferase (UGT) 1A1, an enzyme involved in SN-38 glucuronidation, has been linked to interindividual pharmacokinetic variability and irinotecan toxicity. In addition, variants in other genes encoding drug-metabolizing enzymes or transporters that are involved in the disposition of irinotecan may play a crucial role in the pharmacokinetic and pharmacodynamic profile of irinotecan. In this review, we provide an update on the pharmacogenetics of irinotecan.
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