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Evaluation of hypothermia on the in vitro metabolism and binding and in vivo disposition of midazolam in rats
http://hdl.handle.net/10069/36010
http://hdl.handle.net/10069/36010db52b86b-bb4e-406c-846a-64e40338d7df
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
BDD36_481.pdf (795.2 kB)
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| Item type | 学術雑誌論文 / Journal Article(1) | |||||||||||||||||||||||
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| 公開日 | 2016-11-01 | |||||||||||||||||||||||
| タイトル | ||||||||||||||||||||||||
| タイトル | Evaluation of hypothermia on the in vitro metabolism and binding and in vivo disposition of midazolam in rats | |||||||||||||||||||||||
| 言語 | ||||||||||||||||||||||||
| 言語 | eng | |||||||||||||||||||||||
| キーワード | ||||||||||||||||||||||||
| 主題Scheme | Other | |||||||||||||||||||||||
| 主題 | therapeutic hypothermia | |||||||||||||||||||||||
| キーワード | ||||||||||||||||||||||||
| 主題Scheme | Other | |||||||||||||||||||||||
| 主題 | midazolam | |||||||||||||||||||||||
| キーワード | ||||||||||||||||||||||||
| 主題Scheme | Other | |||||||||||||||||||||||
| 主題 | CYP3A2 | |||||||||||||||||||||||
| キーワード | ||||||||||||||||||||||||
| 主題Scheme | Other | |||||||||||||||||||||||
| 主題 | protein binding | |||||||||||||||||||||||
| キーワード | ||||||||||||||||||||||||
| 主題Scheme | Other | |||||||||||||||||||||||
| 主題 | distribution | |||||||||||||||||||||||
| 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 |
Miyamoto, Hirotaka
× Miyamoto, Hirotaka
× Matsueda, Satoshi
× Moritsuka, Akihiro
× Shimokawa, Kenta
× Hirata, Haruna
× Nakashima, Mikiro
× Sasaki, Hitoshi
× Fumoto, Shintaro
× Nishida, Koyo
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| 抄録 | ||||||||||||||||||||||||
| 内容記述タイプ | Abstract | |||||||||||||||||||||||
| 内容記述 | The effect of hypothermia on the in vivo pharmacokinetics of midazolam was evaluated, with a focus on altered metabolism in the liver and binding to serum proteins. Rat primary hepatocytes were incubated with midazolam (which is metabolized mainly by CYP3A2) at 37, 32 or 28℃. The Michaelis?Menten constant (Km) and maximum velocity (Vmax) of midazolam were estimated using the Michaelis?Menten equation. The Km of CYP3A2 midazolam remained unchanged, but the Vmax decreased at 28℃. In rats, whose temperature was maintained at 37, 32 or 28℃ by a heat lamp or ice pack, the plasma concentrations of midazolam were higher, whereas those in the brain and liver were unchanged at 28℃. The tissue/plasma concentration ratios were, however, increased significantly. The unbound fraction of midazolam in serum at 28?°C was half that at 37℃. These pharmacokinetic changes associated with hypothermic conditions were due to reductions in CYP3A2 activity and protein binding. | |||||||||||||||||||||||
| 書誌情報 |
Biopharmaceutics & Drug Disposition 巻 36, 号 7, p. 481-489, 発行日 2015-10 |
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| 出版者 | ||||||||||||||||||||||||
| 出版者 | John Wiley & Sons, Ltd. | |||||||||||||||||||||||
| ISSN | ||||||||||||||||||||||||
| 収録物識別子タイプ | ISSN | |||||||||||||||||||||||
| 収録物識別子 | 01422782 | |||||||||||||||||||||||
| DOI | ||||||||||||||||||||||||
| 関連タイプ | isVersionOf | |||||||||||||||||||||||
| 識別子タイプ | DOI | |||||||||||||||||||||||
| 関連識別子 | 10.1002/bdd.1960 | |||||||||||||||||||||||
| 権利 | ||||||||||||||||||||||||
| 権利情報 | c 2015 John Wiley & Sons, Ltd. | |||||||||||||||||||||||
| 権利 | ||||||||||||||||||||||||
| 権利情報 | This is the peer reviewed version of the following article: Biopharmaceutics & Drug Disposition, 36(7), pp.481-489; 2015, which has been published in final form at http://dx.doi.org/10.1002/bdd.1960 This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving. | |||||||||||||||||||||||
| 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 | |||||||||||||||||||||||
| 引用 | ||||||||||||||||||||||||
| 内容記述タイプ | Other | |||||||||||||||||||||||
| 内容記述 | Biopharmaceutics & Drug Disposition, 36(7), pp.481-489; 2015 | |||||||||||||||||||||||
