Proficient metabolism of irinotecan by a human intestinal carboxylesterase.
Cancer Res
; 60(17): 4725-8, 2000 Sep 01.
Article
en En
| MEDLINE
| ID: mdl-10987276
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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Base de datos:
MEDLINE
Asunto principal:
Camptotecina
/
Hidrolasas de Éster Carboxílico
/
Intestinos
/
Antineoplásicos Fitogénicos
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Cancer Res
Año:
2000
Tipo del documento:
Article
País de afiliación:
Estados Unidos