title: No toxicity caused by organ accumulation of CPT-11 on multiple injections under clinical regimens in rats.
abstract: We investigated the accumulation of CPT-11 and its metabolite (SN-38) in various organs and toxicities on multiple injections of CPT-11 under clinical regimens in SD rats. CPT-11 (16.7 mg/kg equivalent to 100 mg/m2) was administered intravenously by a single injection, or by multiple injections in 1 course (once a week for three consecutive weeks) or 3 courses (1 course repeated 3 times at intervals of 2 weeks). There was no tendency for CPT-11 and SN-38 to accumulate in any organs regardless of the number of injections. Treatment-related changes were not observed in the general condition, body weight, hematology, biochemistry, and organ weights. Histopathological changes induced by CPT-11 were not persistent and the rats made a rapid recovery after the administrations. From these results, it is suggested that there is no toxicity caused by accumulation of CPT-11 and its active metabolite, SN-38, in organs under clinical regimens in rats.
authors.affiliation: Department of Toxicology, Safety Research Center, Yakult Central Institute for Microbiological Research, 1796 Yaho, Kunitachi-shi, Tokyo 186-8650, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Miura
authors.forename: K
authors.initials: K
authors.lastname: Kaneko
authors.forename: S
authors.initials: S
authors.lastname: Kado
authors.forename: A
authors.initials: A
authors.lastname: Kurita
authors.forename: N
authors.initials: N
authors.lastname: Kaneda
authors.forename: K
authors.initials: K
authors.lastname: Chiba
authors.forename: I
authors.initials: I
authors.lastname: Kato
authors.forename: M
authors.initials: M
authors.lastname: Onoue
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000633:toxicity*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000633:toxicity*; D007267:Injections; D000077146:Irinotecan; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D000077146:Irinotecan; D002166:Camptothecin