Pharmacogenetics of Irinotecan Disposition and Toxicity: A Review

作者：Ken‐ichi Fujita, Alex Sparreboom · 发表于：Current Clinical Pharmacology · 年份：2010 · DOI：10.2174/157488410791498806 · 被引用次数：72 · 研究领域：Cancer therapeutics and mechanisms、Microwave-Assisted Synthesis and Applications、Lung Cancer Research Studies

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.