title: Metabolism of CPT-11. Impact on activity.
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.
authors.affiliation: Sydney Cancer Centre, Royal Prince Alfred Hospital, University of Sydney, Sydney, Australia. lrivory@canc.rpa.cs.nsw.gov.au
authors.forename: L P
authors.initials: LP
authors.lastname: Rivory
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000378:metabolism* / Q000493:pharmacokinetics / Q000494:pharmacology; D001711:Biotransformation; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000493:pharmacokinetics / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000378:metabolism* / Q000493:pharmacokinetics / Q000494:pharmacology; D020719:Glucuronides / Q000378:metabolism; D006801:Humans; D000077146:Irinotecan; D010084:Oxidation-Reduction; D011355:Prodrugs / Q000378:metabolism / Q000493:pharmacokinetics
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004791:Enzyme Inhibitors; D020719:Glucuronides; D011355:Prodrugs; D000077146:Irinotecan; D002166:Camptothecin