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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 |
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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 |