Autor: Noriaki Kuroki, Masahiro Nakano, Akiko Tohgo, Masahiko Kikuchi, Ayumi Kumamoto, Kazuhiko Arimori, Eiji Kumazawa, Naomi Tanoue
Rok vydání: 2001
Předmět:
Zdroj: Pharmaceutical Research. 18:814-822
ISSN: 0724-8741
DOI: 10.1023/a:1011040529881
Popis: Purpose. To investigate the excretion of irinotecan hydrochloride (CPT-11) and its active metabolite, SN-38, into the gastrointestinal lumen via the biliary and/or intestinal membrane route after dosing with lactone and carboxylate forms of CPT-11, and to evaluate the toxic and antitumor effects of the two forms. Methods. The excretions of CPT-11 and SN-38 were investigated by the in situ perfusion technique using rats. The incidence of delayed diarrhea was evaluated after i.v. dosing (60 mg/kg) with CPT-11 lactone and carboxylate forms for 4 days. Antitumor activity and changes in body weight were investigated in mice with Meth A tumors. Results. The excretion of CPT-11 into bile was greater in dosing with CPT-11 carboxylate than that with its lactone form, whereas the exsorption across intestinal membrane was greater in dosing with CPT-11 lactone than that with its carboxylate form. Dosing with CPT-11 lactone dose-dependently inhibited the increase in tumor weights in Meth A tumor mice, whereas the dosing with its carboxylate form reduced the antitumor effect. Conclusions. The decreased antitumor effect caused by dosing with the CPT-11 carboxylate form could be due to less accumulation in the tissue including tumor cells resulting from the rapid elimination of the form in the body.
Databáze: OpenAIRE
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