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Involvement of the Transporters P-Glycoprotein and Breast Cancer Resistance Protein in Dermal Distribution of the Multikinase Inhibitor Regorafenib and Its Active Metabolites
http://hdl.handle.net/2297/48450
http://hdl.handle.net/2297/48450b9736b84-f35c-4642-b1f6-21f7249cb008
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
PH-PR-KATO-Y-2632.pdf (212.7 kB)
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| Item type | 学術雑誌論文 / Journal Article(1) | |||||
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| 公開日 | 2017-12-05 | |||||
| タイトル | ||||||
| タイトル | Involvement of the Transporters P-Glycoprotein and Breast Cancer Resistance Protein in Dermal Distribution of the Multikinase Inhibitor Regorafenib and Its Active Metabolites | |||||
| 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 |
Fujita, Ken-ichi
× Fujita, Ken-ichi× Masuo, Yusuke× Yamazaki, Erina× Shibutani, Toshiki× Kubota, Yutaro× Nakamichi, Noritaka× Sasaki, Yasutsuna× Kato, Yukio |
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| 書誌情報 |
Journal of Pharmaceutical Sciences 巻 106, 号 9, p. 2632-2641, 発行日 2017-09-01 |
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| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 0022-3549 | |||||
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| 収録物識別子タイプ | NCID | |||||
| 収録物識別子 | AA00704450 | |||||
| DOI | ||||||
| 関連タイプ | isVersionOf | |||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.1016/j.xphs.2017.04.064 | |||||
| 出版者 | ||||||
| 出版者 | Elsevier B.V. | |||||
| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Regorafenib is a multikinase inhibitor orally administered to colorectal cancer patients, and is known to often exhibit dermal toxicity. The purpose of this study is to clarify possible involvement of P-glycoprotein and breast cancer resistance protein (BCRP) in the dermal accumulation of regorafenib and its active metabolites M-2 and M-5. Following intravenous administration in triple knockout (Abcb1a/1b/bcrp -/-; TKO) and wild-type (WT) mice, delayed plasma clearance of M-2 and M-5, but not regorafenib, was observed in TKO mice compared to WT mice. Elacridar, an inhibitor of both transporters, also caused delayed clearance of M-2 and M-5, suggesting that these transporters are involved in their elimination. Skin-to-plasma concentration ratios of regorafenib, M-2, and M-5 were significantly higher in TKO mice than in WT mice. Elacridar increased skin-to-plasma and epidermis-to-plasma concentration ratios of regorafenib. Basal-to-apical transport of M-2 and M-5 was observed in LLC-PK1-Pgp and MDCKII/BCRP/PDZK1 cells, which was inhibited by elacridar and the BCRP inhibitor Ko143, respectively. The present findings thus indicate that P-glycoprotein and BCRP are involved in the accumulation of regorafenib and its active metabolites in the skin, by affecting either their systemic exposure or their plasma distribution in the circulating blood. © 2017 American Pharmacists Association®. | |||||
| 内容記述 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | Embargo Period 12 months | |||||
| 権利 | ||||||
| 権利情報 | Copyright © Elsevier (CC-BY NC ND) | |||||
| 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 | URI | |||||
| 関連識別子 | http://www.elsevier.com/locate/issn/00223549 | |||||
