Effect of 5-Fluorouracil Treatment on SN-38 Absorption from Intestine in Rats
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概要
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5-Fluorouracil (5-FU)-based chemotherapies with irinotecan have been applied for the treatment of cancers, and a common dose-limiting toxicity is neutropenia and diarrhea. In this study, we investigated the effect of 5-FU treatment on expression levels of drug transporters for SN-38 transportation and SN-38 absorption from the intestine following 5-FU treatment. Expression levels of several drug transporters and nuclear receptors in rats after 5-FU treatment were evaluated. SN-38 absorption from the intestine was evaluated by SN-38 concentration levels in serum following SN-38 injection into the intestine of 5-FU treated rats. The levels of renal multidrug resistance protein 2 (Mrp2) on day 4 after treatment (400 mg/kg) showed significant upregulation, 359.2 ± 33.2% (mean ± S.E.) of control. Mrp2 levels in the intestine were downregulated to 26.2 ± 8.4% of control. 5-FU treatment (400 mg/kg) also significantly downregurated expression levels of P-glycoprotein (P-gp) and breast cancer resistance protein (Bcrp) to 41.2 ± 14.7%, 15.7 ± 4.3% of control, respectively. To evaluate SN-38 absorption from the intestine, SN-38 was loaded in to the intestine on day 4 after 5-FU treatment. Pretreatment with 5-FU significantly increased SN-38 concentration in the blood 30, 60 and 90 min after SN-38 administration. The area under the curve for SN-38 in the 5-FU group was significantly higher than in vehicle groups. 5-FU treatment decreased expression levels of P-glycoprotein and Bcrp in intestine. The present study suggests that combination chemotherapy of 5-FU with irinotecan (CPT-11) may elevate SN-38 absorption from intestine.
- Pharmaceutical Society of Japanの論文
著者
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Iseki Ken
Laboratory of Clinical Pharmaceutics & Therapeutics, Division of Pharmasciences, Faculty of Pharmace
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Shibayama Yoshihiko
Education Research Center for Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Hokkaido Univer
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Ikeda Ryuji
Department Of Clinical Pharmacy And Pharmacology Graduate School Of Medical And Dental Sciences Kago
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Yamada Katsushi
Department Of Clinical Pharmacology Faculty Of Medicine Kagoshima University
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Kondo Tomoko
Department Of Clinical Pharmacy And Pharmacology Kagoshima University Graduate School Of Medical And
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Kondo Tomoko
Department Of Biology Faculty Of Fisheries Hokkaido University
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Sugawara Mitsuru
Education Res. Center For Clinical Pharmacy Graduate School Of Pharmaceutical Sciences Hokkaido Univ
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Takeda Yasuo
Department Of Cardiac Surgery Kyusyu University School Of Medicine
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Yoshikawa Yoshimi
Department Of Clinical Pharmacy And Pharmacology Graduate School Of Medical And Dental Sciences Kago
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Ikeda Ryuji
Department Of Clinical Pharmacy And Pharmacology Graduate School Of Medical And Dental Sciences Kago
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Iwashita Yoshitaka
Department of Pharmacy, Akune Citizen Hospital
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Osada Takayuki
Education Research Center for Clinical Pharmacy, Graduate School of Pharmaceutical Sciences, Hokkaido University
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Iseki Ken
Laboratory of Clinical Pharmaceutics and Therapeutics, Graduate School of Pharmaceutical Sciences, Hokkaido University
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Ikeda Ryuji
Department of Clinical Pharmacy and Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University
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Sugawara Mitsuru
Education Research Center for Clinical Pharmacy, Graduate School of Pharmaceutical Sciences, Hokkaido University
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Shibayama Yoshihiko
Education Research Center for Clinical Pharmacy, Graduate School of Pharmaceutical Sciences, Hokkaido University
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Yoshikawa Yoshimi
Department of Pharmacy, Takada Hospital
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Ikeda Ryuji
Department of Clinical Pharmacy and Pharmacology Graduate School of Medical and Dental Sciences
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