Metabolism of CPT-11. Impact on activity

Ann N Y Acad Sci. 2000;922:205-15. doi: 10.1111/j.1749-6632.2000.tb07039.x.


Irinotecan (CPT-11) is a semi-synthetic camptothecin with a broad spectrum of clinical activity. It is a prodrug that is cleaved by esterases to the potent topoisomerase I poison, SN-38. In humans, this activation is relatively inefficient, but this may result in a more protracted formation of SN-38 lactone. Some intratumoral activation may also occur, but the significance of this process is uncertain. CPT-11 is metabolized by cytochrome P450 3A to yield a number of comparatively inactive compounds. SN-38 is glucurono-conjugated in the liver, and this metabolite, although inactive, may participate in the enterohepatic cycling of SN-38 after hydrolysis in the intestinal lumen. Overall, the production of SN-38 from CPT-11 is the result of the complex interplay of several metabolic pathways and the source of considerable interpatient variability.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / metabolism*
  • Antineoplastic Agents, Phytogenic / pharmacokinetics
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Biotransformation
  • Camptothecin / analogs & derivatives*
  • Camptothecin / metabolism*
  • Camptothecin / pharmacokinetics
  • Camptothecin / pharmacology
  • Enzyme Inhibitors / metabolism*
  • Enzyme Inhibitors / pharmacokinetics
  • Enzyme Inhibitors / pharmacology
  • Glucuronides / metabolism
  • Humans
  • Irinotecan
  • Oxidation-Reduction
  • Prodrugs / metabolism
  • Prodrugs / pharmacokinetics


  • Antineoplastic Agents, Phytogenic
  • Enzyme Inhibitors
  • Glucuronides
  • Prodrugs
  • Irinotecan
  • Camptothecin