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KAKEN_24590668seika.pdf
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Download
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:654.2 KB
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:Jul 30, 2019 |
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Total downloads since Jul 30, 2019 : 1829
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P450のMBIを介した薬物相互作用に個人差をもたらす遺伝的要因の定量的解明
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P450 ノ MBI オ カイシタ ヤクブツ ソウゴ サヨウ ニ コジンサ オ モタラス イデンテキ ヨウイン ノ テイリョウテキ カイメイ
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P450 no MBI o kaishita yakubutsu sogo sayo ni kojinsa o motarasu identeki yoin no teiryoteki kaimei
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Quantitative analysis of genetic factors affecting the extent of drug interactions via mechanism based inhibition of cytochrome P450
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大谷, 壽一
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オオタニ, ヒサカズ
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Otani, Hisakazu
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慶應義塾大学・薬学部・教授
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Research team head
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科研費研究者番号 : 70262029
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山本, 康次郎
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ヤマモト, コウジロウ
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Yamamoto, Kojiro
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群馬大学・医学部・教授
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Research team member
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科研費研究者番号 : 70174787
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秋好, 健志
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アキヨシ, タケシ
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Akiyoshi, Takeshi
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慶應義塾大学・薬学部・助教
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Research team member
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科研費研究者番号 : 50399143
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山崎, 浩史
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ヤマザキ, ヒロシ
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Yamazaki, Hiroshi
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昭和薬科大学・薬学部・教授
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Research team member
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科研費研究者番号 : 30191274
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2015
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科学研究費補助金研究成果報告書
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2014
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| Abstract |
薬物相互作用 (くすりの飲み合わせ)の起こりやすさには個人差がある。特に, 薬物相互作用の中でも, 薬物酸化代謝酵素であるP450の不可逆的な阻害は, 臨床上問題となっていることから, 本研究では, P450の不可逆的な阻害を介した薬物相互作用のリスクが, 遺伝的な要因によってどの程度影響を受けるかについて, さまざまな遺伝的変異型P450酵素分子(CYP3A4, 2D6変異型)を用いて, in vitro(試験管レベルの)酵素実験を行い, 解析した。その結果, 薬物代謝酵素の阻害を介した薬物相互作用は, さまざまな程度で, 遺伝的要因の影響を受けることが明らかになった。
There seems to be considerable inter-individual variations in the extent of drug interactions, especially via the inhibition of oxidative metabolic enzymes, P450s. This study aimed to investigate quantitatively the influence of genetic variation of P450s, such as CYP3A4 and CYP2D6, on the extent of drug interaction in the in vitro studies using genetic variants. As a result of enzymatic study with probe substrates and mechanism-based inhibitors (MBI), we concluded that the inhibitory potencies of MBI differ among genetic variants. These results suggest that the genetic variation of metabolic enzymes affect the extent of drug interactions caused by their inhibitors, as well as the pharmacokinetics of their substrate drugs.
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研究種目 : 基盤研究(C)
研究期間 : 2012～2014
課題番号 : 24590668
研究分野 : 臨床薬物動態学, 医薬品情報学, 薬物治療の情報科学
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| Jul 29, 2019 | | 著者 を変更 |
| Jul 30, 2019 | | 著者 を変更 |
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