WEKO3
インデックスリンク
アイテム
Species difference in intestinal absorption mechanism of etoposide and digoxin between cynomolgus monkey and rat
http://hdl.handle.net/2297/12346
http://hdl.handle.net/2297/12346efd50ec5-f01f-4550-be31-f8175b0518c5
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
ME-PR-KATO-Y-2467.pdf (688.8 kB)
|
|
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2017-10-03 | |||||
| タイトル | ||||||
| タイトル | Species difference in intestinal absorption mechanism of etoposide and digoxin between cynomolgus monkey and rat | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
| 資源タイプ | journal article | |||||
| 著者 |
Nishimura, T.
× Nishimura, T.× Kato, Yukio× Amano, N.× Ono, M.× Kubo, Yoshiyuki× Kimura, Y.× Fujita, H.× Tsuji, Akira |
|||||
| 提供者所属 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | 金沢大学医薬保健研究域薬学系 金沢大学医薬保健研究域医学系 | |||||
| 書誌情報 |
Pharmaceutical Research 巻 25, 号 11, p. 2467-2476, 発行日 2008-11-01 |
|||||
| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 0724-8741 | |||||
| NCID | ||||||
| 収録物識別子タイプ | NCID | |||||
| 収録物識別子 | AA10632083 | |||||
| DOI | ||||||
| 関連タイプ | isVersionOf | |||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.1007/s11095-008-9658-4 | |||||
| 出版者 | ||||||
| 出版者 | Springer Science+Business Media B.V. | |||||
| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Purpose. The oral bioavailability of some therapeutic agents is markedly lower in cynomolgus monkeys than in humans. We investigated small-intestinal absorption of the P-glycoprotein (P-gp) substrates etoposide and digoxin in monkeys to clarify the influence of efflux transport on their intestinal permeability. Methods. The pharmacokinetics of etoposide and digoxin was examined in monkeys and rats after oral and intravenous administration. Intestinal permeability and segmental differences in permeability were investigated with an Ussing-type chamber. Results. The bioavailability of etoposide was 12.9 and 13.9% in monkeys and rats, respectively. Total body clearance of etoposide in monkeys was much less than hepatic blood flow, suggesting that the bioavailability would be limited at intestinal absorption. Marked vectorial transport of etoposide in the secretory direction was observed in rats, especially in the lower small intestine, and segmental differences were consistent with the distribution of P-gp expression. Vectorial transport was minimal in monkey small intestine. Our kinetic analysis indicated that P-gp contributes little to the intestinal permeability of etoposide and digoxin in monkeys, and apical uptake is rate-limiting. Conclusion. Low bioavailability of etoposide in monkeys is due to poor intestinal uptake resulting from low influx from the apical side, rather than secretion via P-gp. © 2008 Springer Science+Business Media, LLC. | |||||
| 著者版フラグ | ||||||
| 出版タイプ | AM | |||||
| 出版タイプResource | http://purl.org/coar/version/c_ab4af688f83e57aa | |||||
| 関連URI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | http://dx.doi.org/10.1007/s11095-008-9658-4 | |||||
