Format

Send to

Choose Destination
See comment in PubMed Commons below
Ann N Y Acad Sci. 2000;922:205-15.

Metabolism of CPT-11. Impact on activity.

Author information

1
Sydney Cancer Centre, Royal Prince Alfred Hospital, University of Sydney, Sydney, Australia. lrivory@canc.rpa.cs.nsw.gov.au

Abstract

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.

PMID:
11193896
[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Wiley
    Loading ...
    Support Center