Intestinal Cytochrome P450 and Response to Rifampicin in Rabbits

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Properties of cytochrome P450(P450)in rabbit intestines have been investigated to assess the possibility of an experimental model for human intestinal oxidation of drugs.Significant amounts of P450 and cytochrome b<SUB>5</SUB> and activities of NADPH-cytochrome P450 reductase were detected in microsomes from rabbit duodenal, jejunal, ileac and colon mucosa.All the small intestinal fractions mediated phenytoin, dextromethorphan and testosterone oxidations.Several P450 forms belonging to the CYP1A, CYP2C, CYP2D and CYP3A, but not CYP2B and CYP2E, subfamilies were detected in these tissues by Western blotting.A good correlation was observed between immunodetectable levels of CYP3A and activities of testosterone 6β-hydroxylation.Small intestine, but not colon, CYP3A levels were increased by the pretreatment of rabbits with rifampicin(50mg/kg for 4 days, p.o.).The extent of the increase was similar between duodena and livers.These properties of rabbit intestinal P450s were comparable to those of human intestine.These phenomena suggest the possibility that the rabbit is a beneficial in vivo model for the assessment of drug interaction occurring at the first pass of drugs ingested.

収録刊行物

  • The Japanese journal of pharmacology

    The Japanese journal of pharmacology 82(3), 232-239, 2000-03-01

    公益社団法人 日本薬理学会

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各種コード

  • NII論文ID(NAID)
    10008183542
  • 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
    5321051
  • 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  NDL  J-STAGE 
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