Pharmacogenetics of Irinotecan Disposition and Toxicity: A Review

Title: Pharmacogenetics of Irinotecan Disposition and Toxicity: A Review

Volume: 5 Issue: 3

Author(s): Ken-ichi Fujita and Alex Sparreboom

Affiliation:

Keywords: Irinotecan, toxicity, pharmacokinetics, pharmacogenetics, UGT1A1, variability

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.

Cite this article as:

Fujita Ken-ichi and Sparreboom Alex, Pharmacogenetics of Irinotecan Disposition and Toxicity: A Review, Current Clinical Pharmacology 2010; 5 (3) . https://dx.doi.org/10.2174/157488410791498806