Oxidation of Ranitidine by Isozymes of Flavin-Containing Monooxygenase and Cytochrome P450

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Rat and human liver microsomes oxidized ranitidine to its N−oxide(66−76%)and S−oxide(13−18%)and desmethylranitidine(12−16%).N− and S−oxidations of ranitidine were inhibited by metimazole [flavin−containing monooxygenase(FMO)inhibitor] to 96−97% and 71−85%, respectively, and desmethylation of ranitidine was inhibited by SKF525A [cytochrome P450(CYP)inhibitor] by 71−95%.Recombinant FMO isozymes like FMO1, FMO2, FMO3 and FMO5 produced 39, 79, 2180 and 4 ranitinine N−oxide and 45, 0, 580 and 280 ranitinine S−oxide pmol·min<SUP>-1</SUP>·nmol<SUP>-1</SUP> FMO, respectively.Desmethyranitinine was not produced by recombinant FMOs.Production of desmethylranitidine by rat and human liver microsomes was inhibited by tranylcypromine, α−naphthoflavon and quinidine, which are known to inhibit CYP2C19, 1A2 and 2D6, repectively.FMO3, the major form in adult liver, produced both ranitidine N− and S−oxides at a 4 to 1 ratio.FMO1, expressed primarily in human kidney, was 55− and 13−fold less efficient than the hepatic FMO3 in producing ranitidine N− and S−oxides, respectively.FMO2 and FMO5, although expressed slightly in human liver, kidney and lung, were not efficient producers of ranitidine N− and S−oxides.Thus, urinary contents of ranitidine N−oxide can be used as the in vivo probe to determine the hepatic FMO3 activity.

収録刊行物

  • The Japanese journal of pharmacology

    The Japanese journal of pharmacology 84(2), 213-220, 2000-10-01

    公益社団法人 日本薬理学会

参考文献:  31件中 1-31件 を表示

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各種コード

  • NII論文ID(NAID)
    10008185848
  • NII書誌ID(NCID)
    AA00691188
  • 本文言語コード
    ENG
  • 資料種別
    ART
  • ISSN
    00215198
  • NDL 記事登録ID
    5549423
  • NDL 雑誌分類
    ZS51(科学技術--薬学)
  • NDL 請求記号
    Z53-D199
  • データ提供元
    CJP書誌  CJP引用  NDL  J-STAGE 
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