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Impacts of genetic polymorphisms and cancer cachexia on naldemedine pharmacokinetics and bowel movements in patients receiving opioid analgesics
http://hdl.handle.net/10271/0002000327
http://hdl.handle.net/10271/0002000327d18b7599-f7bb-4b50-be3a-333418ca50fc
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
論文本文 (1.3 MB)
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||||||||
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| 公開日 | 2025-02-10 | |||||||||||
| タイトル | ||||||||||||
| タイトル | Impacts of genetic polymorphisms and cancer cachexia on naldemedine pharmacokinetics and bowel movements in patients receiving opioid analgesics | |||||||||||
| 言語 | en | |||||||||||
| 言語 | ||||||||||||
| 言語 | eng | |||||||||||
| キーワード | ||||||||||||
| 主題 | cachexia | |||||||||||
| キーワード | ||||||||||||
| 主題 | genetic polymorphism | |||||||||||
| キーワード | ||||||||||||
| 主題 | naldemedine | |||||||||||
| キーワード | ||||||||||||
| 主題 | opioid-induced constipation | |||||||||||
| キーワード | ||||||||||||
| 主題 | pharmacokinetics | |||||||||||
| 資源タイプ | ||||||||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_db06 | |||||||||||
| 資源タイプ | doctoral thesis | |||||||||||
| 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 | |||||||||||
| その他のタイトル | ||||||||||||
| その他のタイトル | オピオイド鎮痛薬投与患者の遺伝子多型とがん悪液質がナルデメジンの薬物動態および排便に及ぼす影響 | |||||||||||
| 著者 |
中津川, 瑛美
× 中津川, 瑛美
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| 書誌情報 |
en : Fundamental & Clinical Pharmacology 巻 38, 号 3, p. 596-605, 発行日 2024-06 |
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| 出版者 | ||||||||||||
| 出版者 | John Wiley and Sons | |||||||||||
| 言語 | en | |||||||||||
| 権利 | ||||||||||||
| 言語 | en | |||||||||||
| 権利情報 | (C) 2024 The Authors. Fundamental & Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of Société Française de Pharmacologie et de Thérapeutique. | |||||||||||
| 権利 | ||||||||||||
| 言語 | en | |||||||||||
| 権利情報 | This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. | |||||||||||
| 抄録 | ||||||||||||
| 内容記述タイプ | Abstract | |||||||||||
| 内容記述 | Background/Objectives: Clinical responses to naldemedine vary between individuals with advanced cancer. This is a prospective, single-center, observational study aimed to evaluate the influence of genetic polymorphisms and cachexia status on plasma naldemedine and clinical responses. Methods: Forty-eight patients being treated with naldemedine for opioidinduced constipation under treatment of cancer pain were enrolled. Plasma naldemedine concentrations were determined on the fourth day or later after administration of naldemedine, and the associations with genotypes, cachexia status, and clinical responses were assessed. Results: Cancer patients exhibited a large variation in the plasma naldemedine concentrations, and it was correlated with serum total protein level. Patients who were homozygous CYP3A5*3 had a higher plasma concentration of naldemedine than those with the *1 allele. ABCB1 genotypes tested in this study were not associated with plasma naldemedine. A negative correlation was observed between the plasma naldemedine concentration and 4β-hydroxycholesterol level. The plasma naldemedine concentration was lower in patients with refractory cachexia than in those with precachexia and cachexia. While serum levels of interleukin-6 (IL-6) and acute-phase proteins were higher in patients with refractory cachexia, they were not associated with plasma naldemedine. A higher plasma concentration of naldemedine, CYP3A5*3/*3, and an earlier naldemedine administration after starting opioid analgesics were related to improvement of bowel movements. Conclusion: Plasma naldemedine increased under deficient activity of CYP3A5 in cancer patients. Cachectic patients with a higher serum IL-6 had a lower plasma naldemedine. Plasma naldemedine, related to CYP3A5 genotype, and the initiation timing of naldemedine were associated with improved bowel movements. |
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| 言語 | en | |||||||||||
| 学位名 | ||||||||||||
| 学位名 | 博士（医学） | |||||||||||
| 学位の区分 | ||||||||||||
| 内容記述 | doctoral | |||||||||||
| 学位の分野 | ||||||||||||
| 内容記述 | 医学系研究科 | |||||||||||
| 学位授与機関 | ||||||||||||
| 学位授与機関識別子Scheme | kakenhi | |||||||||||
| 学位授与機関識別子 | 13802 | |||||||||||
| 学位授与機関名 | 浜松医科大学 | |||||||||||
| 学位授与機関名 | Hamamatsu University School of Medicine | |||||||||||
| 学位授与年月日 | ||||||||||||
| 学位授与年月日 | 2024-03-13 | |||||||||||
| 学位授与番号 | ||||||||||||
| 学位授与番号 | 甲第983号 | |||||||||||
| ISSN | ||||||||||||
| 収録物識別子タイプ | PISSN | |||||||||||
| 収録物識別子 | 0767-3981 | |||||||||||
| EISSN | ||||||||||||
| 収録物識別子タイプ | EISSN | |||||||||||
| 収録物識別子 | 1472-8206 | |||||||||||
| NII書誌ID | ||||||||||||
| 収録物識別子タイプ | NCID | |||||||||||
| 収録物識別子 | AA10728841 | |||||||||||
| PubMed番号 | ||||||||||||
| 関連タイプ | isIdenticalTo | |||||||||||
| 識別子タイプ | PMID | |||||||||||
| 関連識別子 | 38192190 | |||||||||||
| 出版社DOI | ||||||||||||
| 関連タイプ | isIdenticalTo | |||||||||||
| 識別子タイプ | DOI | |||||||||||
| 関連識別子 | https://doi.org/10.1111/fcp.12976 | |||||||||||
| 著者版フラグ | ||||||||||||
| 出版タイプ | VoR | |||||||||||
| 出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||||||||
