Metabolism of irinotecan to SN-38 in a tissue-isolated tumor model

Biological & Pharmaceutical Bulletin
R AtsumiH Hakusui

Abstract

The objective of this study is to investigate the metabolism of the antitumor drug, irinotecan (CPT-11), to its active metabolite, SN-38, in tumor tissue. Using Walker 256 carcinoma, we prepared a tissue-isolated tumor model: tumor preparation was continuously perfused with Krebs-Henseleit bicarbonate buffer containing 4% bovine serum albumin (BSA) and CPT-11 (10 micrograms/ml), and the concentration of SN-38 in the perfusate was monitored using HPLC. The concentration of SN-38 in the perfusate was gradually increased to a level of 9.69 ng/ml 60 min after the start of perfusion. As a control, an aliquot of the perfusate was separately incubated; however, no significant increase in SN-38 levels was observed. At the end of the perfusion, a part of the tumor tissue was homogenized and the level of SN-38 was determined; the levels in tumor tissue were 2.2-4.5 times higher than in the perfusate. From above results, CPT-11 was found to be metabolized to its active metabolite, SN-38, in tumor tissue--a desirable feature of an antitumor prodrug.

Citations

Jan 20, 2004·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·H WildiersA T van Oosterom
May 22, 2010·Neuro-oncology·Peter J DickinsonKrystof S Bankiewicz
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Jan 7, 2000·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·M J de JongeA Sparreboom
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