Pharmacogenetics of irinotecan metabolism and transport: An update

Nicola F. Smith, William D. Figg*, Alex Sparreboom

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

163 Scopus citations


The anticancer agent irinotecan (CPT-11) is converted to SN-38, which is approximately 100 to 1000-fold more cytotoxic than the parent drug. The pharmacokinetics of irinotecan are extremely complex and have been the subject of intensive investigation in recent years. Irinotecan is subject to extensive metabolism by various polymorphic enzymes, including CES2 to form SN-38, members of the UGT1A subfamily, and CYP3A4 and CYP3A5, which form several pharmacologically inactive oxidation products. Elimination of irinotecan is also dependent on drug-transporting proteins, notably ABCB1 (P-glycoprotein), ABCC2 (cMOAT) and ABCG2 (BCRP), present on the bile canalicular membrane. The various processes mediating drug elimination, either through metabolic breakdown or excretion, likely impact substantially on interindividual variability in drug handling. This report provides an update on current strategies to individualize irinotecan chemotherapy based on each patient's genetic constitution, which may ultimately lead to more selective use of this agent.

Original languageEnglish
Pages (from-to)163-175
Number of pages13
JournalToxicology in Vitro
Issue number2
StatePublished - Mar 2006
Externally publishedYes


  • ABCB1
  • ABCC1
  • ABCC2
  • ABCG2
  • CES
  • CPT-11
  • CYP3A
  • SN-38
  • UGT1A


Dive into the research topics of 'Pharmacogenetics of irinotecan metabolism and transport: An update'. Together they form a unique fingerprint.

Cite this