In vivo-In vitro Relationship of Methotrexate 7-Hydroxylation by Aldehyde Oxidase in Four Different Strain Rats

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著者

    • MORIYASU Aya
    • Division of Medicinal Chemistry, Graduate School of Biomedical Sciences, Hiroshima University
    • SUGIHARA Kazumi
    • Division of Medicinal Chemistry, Graduate School of Biomedical Sciences, Hiroshima University
    • NAKATANI Keiko
    • Division of Medicinal Chemistry, Graduate School of Biomedical Sciences, Hiroshima University
    • OHTA Shigeru
    • Division of Medicinal Chemistry, Graduate School of Biomedical Sciences, Hiroshima University
    • KITAMURA Shigeyuki
    • Division of Medicinal Chemistry, Graduate School of Biomedical Sciences, Hiroshima University

抄録

  The <i>in vivo</i> metabolism of methotrexate (MTX) to 7-hydroxymethotrexate (7-OH-MTX) was studied using four strains of rats. When MTX was administered to these rats, 7-OH-MTX was detected as the major <i>in vivo</i> metabolite, mainly in bile and feces, and also slightly in the urine. There were marked strain differences in the amounts of 7-OH-MTX excreted in bile, feces and urine. The highest recovery of 7-OH-MTX in bile, feces and urine was observed in Sea:SD rats (6.2%, 4.2% and 0.8% of dose, respectively), followed by Jcl:SD and Crj:SD rats. The lowest recovery (0.02%, 0.2% and 0.003%, respectively) was observed in WKA/Sea rats. The variations of excreted amount of 7-OH-MTX were closely correlated with the strain differences of cytosolic MTX 7-hydroxylase and benzaldehyde oxidase activities. Our results indicate that variation of formation of 7-OH-MTX from MTX <i>in vivo</i> in rats is due primarily to variation of aldehyde oxidase.<br>

収録刊行物

  • Drug metabolism and pharmacokinetics  

    Drug metabolism and pharmacokinetics 21(6), 485-491, 2006-12-25 

    The Japanese Society for the Study of Xenobiotics

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各種コード

  • NII論文ID(NAID)
    10018658997
  • NII書誌ID(NCID)
    AA1162652X
  • 本文言語コード
    ENG
  • 資料種別
    ART
  • ISSN
    13474367
  • データ提供元
    CJP書誌  CJP引用  J-STAGE 
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