小腸代謝研究の現状と問題点

• 小村 弘

  バイエル薬品中央研究所・薬物動態分野・探索代謝研究

書誌事項

タイトル別名

• Current Status and Critical Issues on the Investigation of Small Intestinal Metabolism.

抄録

Recently, pharmacokinetic analysis in clinical study has indicated that small intestinal metabolisms of certain drugs give a great impact on their exposures due to extensive first-pass effects particularly by CYP3A4. However, the in vitro metabolic activities in the small intestinal microsomes are, in general, lower than the relevant hepatic activities, and the intestinal extraction ratio predicted from the activities appeared to be inconsistent with the in vivo data. The reason for this may lie in the fact that both methodologies for the estimations from in vitro and in vivo have some issues (involvement of protein binding and effect of inducers/inhibitors on Q, respectively) to be clarified, or P-glycoprotein with the similar substrate specificity to CYP3A might be involved in the first pass metabolism. The detailed studies in an animal with a comparable CYP3A activity to human will be required to elucidate the contribution of small intestinal first-pass to overall metabolism.

収録刊行物

• 薬物動態

  薬物動態 15 (2), 159-164, 2000

  日本薬物動態学会

キーワード

• Small intestinal metabolism
• First-pass metabolism
• P450s
• CYP3A
• P-glycoprotein
• Species difference

詳細情報

• CRID: 1390282679646969984
• NII論文ID: 10008415995
• NII書誌ID: AN10144117
• DOI: 10.2133/dmpk.15.159
• ISSN: 09161139
• Web Site: http://www.jstage.jst.go.jp/article/dmpk1986/15/2/15_2_159/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2000221399
• 本文言語コード: ja
• データソース種別:
  • JaLC
  • Crossref
  • CiNii Articles
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