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

Lessons learned from the irinotecan metabolic pathway.

M K Ma1, H L McLeod

  • 1Washington University School of Medicine, Department of Medicine, St Louis, MO 63110, USA.

Current Medicinal Chemistry
|February 7, 2003
PubMed
Summary

Irinotecan variability in cancer treatment is due to complex metabolism and drug interactions. Understanding these pathways, including activation and detoxification, can optimize irinotecan therapy and reduce side effects.

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

Anisotropic Two-Dimensional Disordered Wigner Solid.

Physical review letters·2022
Same author

Spontaneous Valley Polarization of Itinerant Electrons.

Physical review letters·2021
Same author

Observation of spontaneous ferromagnetism in a two-dimensional electron system.

Proceedings of the National Academy of Sciences of the United States of America·2020
Same author

Precise Experimental Test of the Luttinger Theorem and Particle-Hole Symmetry for a Strongly Correlated Fermionic System.

Physical review letters·2020
Same author

Gene expression and linkage analysis implicate CBLB as a mediator of rituximab resistance.

The pharmacogenomics journal·2017
Same author

Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for CYP2C19 and Voriconazole Therapy.

Clinical pharmacology and therapeutics·2016

Area of Science:

  • Pharmacology
  • Oncology
  • Drug Metabolism

Background:

  • Irinotecan, a topoisomerase I poison, treats various solid tumors but shows significant inter-patient variability.
  • Unpredictable severe diarrhea and complex metabolic pathways limit irinotecan's clinical utility.
  • Genetic variations in irinotecan-metabolizing enzymes contribute to disposition variability.

Purpose of the Study:

  • To review the latest findings on irinotecan's complex pharmacology.
  • To elucidate drug activation, transport, glucuronidation, and CYP3A-mediated drug-drug interactions.
  • To provide insights for optimizing irinotecan therapy and future research.

Main Methods:

  • Literature review of clinical pharmacology studies on irinotecan.
  • Analysis of metabolic pathways including CYP3A4, carboxylesterase, and UGT1A1.

Related Experiment Videos

  • Investigation of drug transporter involvement and drug-drug interactions.

    • Main Results:

    • Irinotecan is bioactivated to SN-38 via carboxylesterase and detoxified by UGT1A1.
    • CYP3A4 mediates oxidative metabolism to inactive metabolites.
    • Genetic polymorphisms in CYP3A4 and UGT1A1, drug transporters, and drug-drug interactions significantly impact irinotecan disposition.

    Conclusions:

    • Optimizing irinotecan therapy requires a comprehensive understanding of its activation, metabolism, and transport.
    • Addressing inter-individual variability through pharmacogenetic and drug interaction studies is crucial.
    • Further research into irinotecan's complex pharmacology can enhance its therapeutic efficacy and safety.