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Association of axitinib plasma exposure and genetic polymorphisms of ABC transporters with axitinib-induced toxicities in patients with renal cell carcinoma
http://hdl.handle.net/2237/25613
http://hdl.handle.net/2237/25613817b9711-8892-476c-b91d-ec6ccffe374c
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
article.pdf ファイル公開：2017/09/01 (291.1 kB)
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| アイテムタイプ | 学術雑誌論文 / Journal Article(1) | |||||
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| 公開日 | 2017-02-20 | |||||
| タイトル | ||||||
| タイトル | Association of axitinib plasma exposure and genetic polymorphisms of ABC transporters with axitinib-induced toxicities in patients with renal cell carcinoma | |||||
| 言語 | en | |||||
| 著者 |
Kato, Hiroshi
× Kato, Hiroshi× Sassa, Naoto× Miyazaki, Masayuki× Takeuchi, Mio× Asai, Miho× Iwai, Akane× Noda, Yukihiro× Gotoh, Momokazu× Yamada, Kiyofumi |
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| アクセス権 | ||||||
| アクセス権 | open access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||
| 権利 | ||||||
| 権利情報 | The final publication is available at Springer via http://doi.org/10.1007/s00595-016-1342-4 | |||||
| 言語 | en | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | Axitinib | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | Renal cell carcinoma | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | Pharmacokinetics | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | Adverse events | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | ABCG2 | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | ABCB1 | |||||
| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Purpose: Axitinib is a selective tyrosine kinase inhibitor of VEGF receptors, approved for advanced renal cell carcinoma (RCC). Associations between axitinib plasma exposure, genetic polymorphisms of ABC transporters and axitinib-induced toxicities have not been adequately explored. Methods: Twenty RCC patients treated with axitinib were enrolled in this study. Blood samples were collected 0, 0.5, 1, 2, 4, and 6 h after administration of axitinib on day 1 and at steady state. Plasma concentrations of axitinib were analyzed by UPLC–MS/MS. The ABCG2 (421C>A) and ABCB1 (1236C>T, 2677G>T/A, 3435C>T) genetic polymorphisms were determined by real-time PCR. Results: ABCB1 haplotype was associated with increased dose-adjusted area under the plasma concentration–time curve (AUC) of axitinib at steady state. The incidence of fatigue during therapy was associated with high AUC0–6 of axitinib (P = 0.013). The treatment period without discontinuation or dose reduction due to adverse events in patients with high AUC0–6 of axitinib was significantly shorter than for those with low AUC0–6 (P = 0.024). No significant differences were found in the frequency of adverse events among the ABCG2 genotype and ABCB1 haplotype groups. Conclusions: Our results have demonstrated that adverse events leading to discontinuation or dose reduction in axitinib were associated with increased axitinib plasma exposure, but not directly with genetic polymorphisms of ABC transporters. Therefore, measurement of steady state axitinib plasma concentrations may be useful in avoiding adverse events in axitinib therapy. | |||||
| 言語 | en | |||||
| 内容記述 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | First Online:01 September 2016 | |||||
| 言語 | en | |||||
| 出版者 | ||||||
| 出版者 | Springer | |||||
| 言語 | en | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプresource | http://purl.org/coar/resource_type/c_6501 | |||||
| タイプ | journal article | |||||
| 出版タイプ | ||||||
| 出版タイプ | AM | |||||
| 出版タイプResource | http://purl.org/coar/version/c_ab4af688f83e57aa | |||||
| DOI | ||||||
| 関連タイプ | isVersionOf | |||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | https://doi.org/10.1007/s00280-016-3145-0 | |||||
| ISSN | ||||||
| 収録物識別子タイプ | PISSN | |||||
| 収録物識別子 | 0344-5704 | |||||
| 書誌情報 |
en : Cancer Chemotherapy and Pharmacology 巻 78, 号 4, p. 855-862, 発行日 2016-10 |
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| 著者版フラグ | ||||||
| 値 | author | |||||
| URI | ||||||
| 識別子 | http://doi.org/10.1007/s00280-016-3145-0 | |||||
| 識別子タイプ | DOI | |||||
| URI | ||||||
| 識別子 | http://hdl.handle.net/2237/25613 | |||||
| 識別子タイプ | HDL | |||||
