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Updated: Sep 29, 2026

Mass Spectrometry and Luminogenic-based Approaches to Characterize Phase I Metabolic Competency of In Vitro Cell Cultures
Published on: March 28, 2017
Proficient metabolism of irinotecan by a human intestinal carboxylesterase
R Khanna1, C L Morton, M K Danks
1Department of Molecular Pharmacology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
Abstract:
Irinotecan [7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin (CPT-11)] is metabolized by esterases to yield the potent topoisomerase I poison 7-ethyl-10-hydroxycamptothecin. One of the major side effects observed with CPT-11 is gastrointestinal toxicity, and we supposed that this might be due to local activation of CPT-11 within the gut. Carboxylesterase (CE) activity was detected in human gut biopsies, and extracts of these tissues converted CPT-11 to 7-ethyl-10-hydroxycamptothecin in vitro. Expression of a human intestinal CE cDNA in COS-7 cells produced extracts that demonstrated proficient CPT-11 activation and conferred sensitivity of cells to CPT-11. These results suggest that gut toxicity from CPT-11 may be due in part to direct drug conversion by CEs present within the small intestine.
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