Excretion into gastrointestinal tract of irinotecan lactone and carboxylate forms and their pharmacodynamics in rodents

摘要: Purpose. To investigate the excretion of irinotecan hydrochloride (CPT-11) and its active metabolite, SN-38, into gastrointestinal lumen via biliary and/or intestinal membrane route after dosing with lactone carboxylate forms CPT-11, to evaluate toxic antitumor effects two forms. Methods. The excretions CPT-11 SN-38 were investigated by in situ perfusion technique using rats. incidence delayed diarrhea was evaluated i.v. (60 mg/kg) for 4 days. Antitumor activity changes body weight mice Meth A tumors. Results. bile greater than that form, whereas exsorption across form. Dosing dose-dependently inhibited increase tumor weights mice, form reduced effect. Conclusions. decreased effect caused could be due less accumulation tissue including cells resulting from rapid elimination body.