Theory Based Analysis of Anti-Inflammatory Effect of Infliximab on Crohn's Disease

• FURUYA Yoko

  Department of Clinical Evaluation of Drug Efficacy, Tokyo University of Pharmacy and Life Science

• OZEKI Takeshi

  Department of Clinical Evaluation of Drug Efficacy, Tokyo University of Pharmacy and Life Science

• TAKAYANAGI Risa

  Department of Clinical Drug Evaluation, School of Pharmacy, Tokyo University of Pharmacy and Life Science

• YOKOYAMA Haruko

  Department of Clinical Drug Evaluation, School of Pharmacy, Tokyo University of Pharmacy and Life Science

• OKUYAMA Kiyoshi

  Department of Clinical Evaluation of Drug Efficacy, Tokyo University of Pharmacy and Life Science

• YAMADA Yasuhiko

  Department of Clinical Evaluation of Drug Efficacy, Tokyo University of Pharmacy and Life Science

抄録

  Tumor necrosis factor (TNF)-α, a primary mediator of inflammatory responses, is increased in patients with active Crohn's disease (CD) and considered to play an important role in the regulation of inflammation in CD. Infliximab (IFX) is a chimeric murine-human monoclonal IgG1 antibody that targets TNF-α and is used as a therapeutic agent for CD. Although that dosage regimen has been established through clinical trial experience, it has not been analyzed theoretically. We analyzed of sequential changes of the Crohn's disease activity index (CDAI) using a pharmacokinetic-pharmacodynamic model integrating the pharmacokinetics of IFX and turnover rate of TNF-α. The time course effects of IFX derived from the present model were matched to reported data regarding CDAI ratios, and we found that the clinical effect of IFX reached a maximum value 2 to 4 weeks after administration and was maintained for the next several weeks. Our results suggested that the standard dosage regimen of IFX is theoretically appropriate. Further, based on the results of various dosage regimens, a second administration of IFX 2 weeks after the first dose was shown to achieve remission in the early stage of active CD, when IFX was given as a repeated treatment.<br>

収録刊行物

• Ｄｒｕｇ　Ｍｅｔａｂｏｌｉｓｍ　ａｎｄ　Ｐｈａｒｍａｃｏｋｉｎｅｔｉｃｓ

  Ｄｒｕｇ　Ｍｅｔａｂｏｌｉｓｍ　ａｎｄ　Ｐｈａｒｍａｃｏｋｉｎｅｔｉｃｓ 22 (1), 20-25, 2007

  日本薬物動態学会

キーワード

• tumor necrosis factor-α
• Crohn's disease activity index
• pharmacokinetic-pharmacodynamic model

詳細情報

• CRID: 1390282680155858048
• NII論文ID: 10018732887
• NII書誌ID: AA1162652X
• DOI: 10.2133/dmpk.22.20
• ISSN: 18800920
• ISSN: 13474367
• Web Site: http://api.elsevier.com/content/article/PII:S1347436715302287?httpAccept=text/xml
• Web Site: http://api.elsevier.com/content/article/PII:S1347436715302287?httpAccept=text/plain
• Web Site: https://search.jamas.or.jp/link/ui/2007232881
• 本文言語コード: en
• データソース種別:
  • JaLC
  • Crossref
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可