|
Hokkaido University Collection of Scholarly and Academic Papers >
Faculty of Pharmaceutical Sciences >
Peer-reviewed Journal Articles, etc >
Effect of 5-Fluorouracil Treatment on SN-38 Absorption from Intestine in Rats
| 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 | | SN-38 | | irinotecan | | absorption | | neutropenia | | diarrhea |
| 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 |
| URI: | http://hdl.handle.net/2115/47205 |
| 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
|
