Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

Irinotecan (CPT-11): a brief overview

L P Rivory1

  • 1University of Queensland, Department of Medicine, Princess Alexandra Hospital, Woolloongabba, Australia.

Clinical and Experimental Pharmacology & Physiology
|October 1, 1996
PubMed
Summary

Irinotecan, a prodrug of SN-38, shows anti-cancer activity by inhibiting topoisomerase I. Its efficacy and toxicity are influenced by metabolism and pharmacogenetics.

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Pemetrexed pharmacokinetics and pharmacodynamics in a phase I/II study of doublet chemotherapy with vinorelbine: implications for further optimisation of pemetrexed schedules.

British journal of cancer·2007
Same author

Imatinib disposition and ABCB1 (MDR1, P-glycoprotein) genotype.

Clinical pharmacology and therapeutics·2007
Same author

Wash-in methodology and modeling to determine hepatocellular D-glucose transport in the perfused rat liver.

The Japanese journal of physiology·2005
Same author

Carbon monoxide disposition and permeability-surface area product in the foetal circulation of the perfused term human placenta.

Placenta·2002
Same author

Hepatic cytochrome P450 3A drug metabolism is reduced in cancer patients who have an acute-phase response.

British journal of cancer·2002
Same author

Highly sensitive analysis of the antifolate pemetrexed sodium, a new cancer agent, in human plasma and urine by high-performance liquid chromatography.

Journal of chromatography. B, Biomedical sciences and applications·2002

Area of Science:

  • Pharmacology
  • Oncology
  • Molecular Biology

Background:

  • Irinotecan (CPT-11) is a semi-synthetic camptothecin analogue with broad anti-tumour activity.
  • It functions by stabilizing the topoisomerase I-DNA complex, leading to DNA damage and cell death.
  • Irinotecan is a prodrug, with its active metabolite SN-38 exhibiting greater potency.

Purpose of the Study:

  • To elucidate the mechanism of action and metabolism of irinotecan.
  • To understand the stereoselective synthesis and activity of irinotecan and its metabolite SN-38.
  • To explore the factors contributing to irinotecan's unique toxicities.

Main Methods:

  • Analysis of irinotecan's interaction with topoisomerase I and DNA.
  • Investigation of irinotecan's metabolic pathways, including carboxylesterase-mediated conversion to SN-38.
  • Evaluation of the stereochemistry of camptothecin analogues.

Main Results:

  • Irinotecan stabilizes the topoisomerase I-DNA complex, causing DNA strand breaks.
  • SN-38 is a more potent metabolite, but its formation from irinotecan is inefficient in humans.
  • Irinotecan exhibits stereoselectivity at C-20, with the (S)-configuration being crucial for activity.
  • Metabolism of irinotecan and SN-38 involves reactions subject to pharmacogenetic variability.
  • Therapy is linked to cholinergic toxicity (acetylcholinesterase inhibition) and delayed diarrhea.

Conclusions:

  • Irinotecan's anti-cancer efficacy relies on its conversion to SN-38 and subsequent topoisomerase I inhibition.
  • Metabolic inefficiency and pharmacogenetic factors may influence irinotecan's therapeutic index.
  • Understanding irinotecan's metabolism and toxicity is crucial for optimizing cancer therapy.

Related Experiment Videos