Drug Metabolism and Pharmacokinetics
Online ISSN : 1880-0920
Print ISSN : 1347-4367
ISSN-L : 1347-4367
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Theory Based Analysis of Anti-Inflammatory Effect of Infliximab on Crohn's Disease
Yoko FURUYATakeshi OZEKIRisa TAKAYANAGIHaruko YOKOYAMAKiyoshi OKUYAMAYasuhiko YAMADA
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2007 Volume 22 Issue 1 Pages 20-25

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Abstract
  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.
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© 2007 by The Japanese Society for the Study of Xenobiotics
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