2026-03-08T13:15:41Z https://kumadai.repo.nii.ac.jp/oai

oai:kumadai.repo.nii.ac.jp:00022635 2024-12-27T02:50:05Z 415:416

Co-administration of irinotecan decreases the plasma concentration of an active metabolite of amrubicin, amrubicinol in rats Maeda, Yukiko 前田, 由紀子 マエダ, ユキコ Hamada, Akinobu 濱田, 哲暢 ハマダ, アキノブ Sanematsu, Emiko 實松, 絵美子 サネマツ, エミコ Sasaki, Jiichiro 佐々木, 治一郎 ササキ, ジイチロウ Yokoo, Koji Hira, Asumi Saito, Hideyuki 齋藤, 秀之 サイトウ, ヒデユキ open access (C) Springer-Verlag 2009 499 Amrubicin Amrubicinol Irinotecan Drug–drug interaction PURPOSE: This study examined the pharmacokinetics of irinotecan (CPT-11), active metabolite 7-ethyl-10-hydroxycamptothecin (SN-38), SN-38 glucuronide (SN-38G) amrubicin (AMR), and active metabolite amrubicinol (AMR-OH) after intravenous administration of this combination therapy in rats. METHODS: Male Sprague-Dawley rats were treated with 10 mg/kg CPT-11 with 10 mg/kg AMR. AMR, AMR-OH, CPT-11, SN-38 and SN-38G were measured in plasma, bile, and tissues using high-performance liquid chromatography. RESULTS: Co-administration of CPT-11 resulted in a significant decrease in plasma concentrations and area under the curves (AUC) of AMR-OH compared with treatment with AMR alone. On the other hand, co-administration of AMR resulted in a slight increase in the initial plasma concentration of SN-38; however, there were no differences in AUC values in CPT-11 and SN-38. The cumulative biliary excretion curves of AMR, CPT-11, and their active metabolites were not changed. CPT-11 inhibited the conversion of AMR to AMR-OH in rat cytosolic fractions. CONCLUSIONS: CPT-11 did not affect the pharmacokinetic of AMR but decreased the plasma concentration of AMR-OH and might affect the formation of AMR-OH from AMR in hepatocytes. Springer Berlin 2009-08-21 eng journal article AM http://hdl.handle.net/2298/15930 https://kumadai.repo.nii.ac.jp/records/22635 https://doi.org/10.1007/s00280-009-1102-x 0344-5704 Cancer Chemotherapy and Pharmacology 65 953 959 https://kumadai.repo.nii.ac.jp/record/22635/files/CCP-MAEDA20090821_r.pdf application/pdf 248.2 kB 2020-03-02