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Effect of 5-Fluorouracil Treatment on SN-38 Absorption from Intestine in Rats

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Title: Effect of 5-Fluorouracil Treatment on SN-38 Absorption from Intestine in Rats
Authors: Shibayama, Yoshihiko Browse this author
Iwashita, Yoshitaka Browse this author
Yoshikawa, Yoshimi Browse this author
Kondo, Tomoko Browse this author
Ikeda, Ryuji Browse this author
Takeda, Yasuo Browse this author
Osada, Takayuki Browse this author
Sugawara, Mitsuru Browse this author
Yamada, Katsushi Browse this author
Iseki, Ken Browse this author
Keywords: 5-fluorouracil
Issue Date: Sep-2011
Publisher: Pharmaceutical Society of Japan
Journal Title: Biological & Pharmaceutical Bulletin
Volume: 34
Issue: 9
Start Page: 1418
End Page: 1425
Publisher DOI: 10.1248/bpb.34.1418
Abstract: 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.
Type: article
Appears in Collections:薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 柴山 良彦

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