Pharmacogenetics of irinotecan disposition and toxicity: a review.
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.
Fujita
Ken-ichi
K
Department of Pharmaceutical Sciences, St. Jude Children's Research Hospotal, Memphis, TN 38105-3678, USA.
Sparreboom
Alex
A
D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects* / Q000493:pharmacokinetics*; D002166:Camptothecin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D014453:Glucuronosyltransferase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D000077146:Irinotecan; D009503:Neutropenia / Q000139:chemically induced*; D011110:Polymorphism, Genetic; D000099148:UGT1A1 Enzyme
D000972:Antineoplastic Agents, Phytogenic; D002166:Camptothecin; D014453:Glucuronosyltransferase; D000077146:Irinotecan; D000099148:UGT1A1 Enzyme