title: Metabolism of irinotecan to SN-38 in a tissue-isolated tumor model.
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.
authors.affiliation: Drug Metabolism & Analytical Chemistry Research Center, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan.
authors.forename: R
authors.initials: R
authors.lastname: Atsumi
authors.forename: O
authors.initials: O
authors.lastname: Okazaki
authors.forename: H
authors.initials: H
authors.lastname: Hakusui
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000378:metabolism*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000378:metabolism; D002279:Carcinoma 256, Walker / Q000378:metabolism*; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D005260:Female; D000077146:Irinotecan; D010051:Ovarian Neoplasms / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014407:Tumor Cells, Cultured
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D000077146:Irinotecan; D002166:Camptothecin