化学反応性に起因する薬物毒性メカニズムの多様性 Diversity in Chemical Mechanisms Involved in Drug Toxicity Caused by Chemically Reactive Species

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著者

    • 村井 孝弘 MURAI Takahiro
    • 第一三共株式会社 薬物動態研究所 Drug Metabolism and Pharmacokinetics Research Laboratories, Daiichi Sankyo Co., Ltd.

抄録

A large number of electrophilic reactive metabolites, such as quinone derivatives, Michael acceptors, nitrogen-containing electrophiles, and epoxides, are produced from drug candidates by drug-metabolizing enzymes, mainly cytochrome P450s. However, reactive metabolites are very unstable and can only be detected after being trapped by nucleophiles. Glutathione and its derivatives are the most utilized nucleophilic trapping reagents. Glutathione-trapped reactive metabolites can be detected by various methods using liquid chromatography-mass spectrometry. Moreover, some drug compounds are naturally chemically reactive to a certain extent. These include β-lactam antibiotics and sulfhydryl-containing drugs. Our study on rofecoxib, a cyclooxygenase-2 inhibitor withdrawn from the market in 2004, suggests that it is a nucleophilic reactive drug that reacts with the aldehyde group of allysine, thereby preventing the formation of cross-linkages in elastin and causing degradation of the elastic fibers in the aorta.

収録刊行物

  • 質量分析 = Mass spectroscopy  

    質量分析 = Mass spectroscopy 56(3), 151-154, 2008-06-01 

    The Mass Spectrometry Society of Japan

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各種コード

  • NII論文ID(NAID)
    10021086949
  • NII書誌ID(NCID)
    AN0010555X
  • 本文言語コード
    JPN
  • 資料種別
    REV
  • ISSN
    13408097
  • NDL 記事登録ID
    9541386
  • NDL 雑誌分類
    ZP4(科学技術--化学・化学工業--分析化学)
  • NDL 請求記号
    Z17-213
  • データ提供元
    CJP書誌  NDL  J-STAGE 
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