CYP2D6-Mediated Mexiletine-Protein Adduct Formation
スポンサーリンク
概要
- 論文の詳細を見る
An antiarrhythmic drug mexiletine, which is metabolized by CYP2D6 and, to a lesser extent, by CYP1A2, is known to sometimes induce allergic reactions. Since mexiletine itself is chemically inert, metabolic activation of the drug, required for the formation of protein adduct, is thought to be a first step in the induction of the allergic reactions. In the present study, we screened several cytochrome P450 (CYP) enzymes for their ability to form protein adducts with mexiletine. Of the 10 CYPs examined (CYP1A1, 1A2, 2A6, 2B6, 2C9, 2C19, 2D6, 2E1, 3A4 and 3A5), CYP2D6 was most efficient in adduct formation with microsomal proteins. On autoradiographs of SDS-PAGE-separated proteins, a 52 kDa band was detected in the CYP2D6-expressing microsomes. These results suggest that the mexiletine-protein adduct is formed mainly by CYP2D6-dependent metabolic activation.
- 公益社団法人日本薬学会の論文
- 2004-02-01
著者
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Maekawa Keiko
Project Team For Pharmacogenetics National Institute Of Health Sciences
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Maekawa Keiko
Division Of Drug Evaluation National Institute Of Health Sciences Osaka Branch
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SAEKI Mayumi
Project Team for Pharmacogenetics, National Institute of Health Sciences
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HACHISUKA Akiko
Division of Biochemistry and Immunochemistry, National Institute of Health Sciences
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Saeki Mayumi
国立医薬品食品衛生研究所 機能生化学部
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Saeki Mayumi
Project Team For Pharmacogenetics National Institute Of Health Sciences
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Hachisuka Akiko
Division Of Biochemistry And Immunochemistry National Institute Of Health Sciences
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Hachisuka Akiko
国立医薬品食品衛生研究所
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Hachisuka Akiko
National Institute Of Health Sciences
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Teshima Reiko
Division of Biochemistry and Immunochemistry, National Institute of Health Sciences
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OZAWA Shogo
Division of Pharmacology, National Institute of Health Sciences
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Saka Makoto
国立がんセンター中央病院 腫瘍内科
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Sasako Mitsuru
国立がんセンター中央病院 腫瘍内科
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Sasako Mitsuru
Surgical Division National Cancer Center Hospital
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Yoshida Shigeaki
国立がんセンター東病院 消化管内科
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Manabe Kasumi
鳥取大学 医学系研究科再生医療学
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Matsuura Kaoru
国立循環器病センター
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Sawada Jun-ichi
Division Of Functional Biochemistry And Genomics National Institute Of Health Sciences
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SASAKI Yasutsuna
National Cancer Center Hospital East
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Ozawa Shogo
Division Of Pharmacology National Institute Of Health Sciences
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Saito Yoshiro
Division Of Gastrointestinal Oncology National Cancer Center Hospital
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Saito Yoshiro
Division Of Biochemistry And Immunochemistry National Institute Of Health Science
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Maekawa Keiko
Division Of Biochemistry And Immunochemistry National Institute Of Health Sciences
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Sawada Jun-ichi
Division Of Biochemistry And Immunochemistry Natinal Institute Of Health Sciences
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Teshima Reiko
National Institute Of Health Science
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Teshima Reiko
Division Of Biochemistry And Immunochemistry National Institute Of Health Sciences
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Ozawa Shogo
National Institute Of Health Sciences
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Ozawa Shogo
Project Team For Pharmacogenetics National Inst. Of Health Sciences
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Okada Shuichi
Hepatobiliary And Pancreatic Oncology Division National Cancer Center Hospital
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