Of infliximab with long-term administration in Japanese patients with Crohn's disease: Analysis using population pharmacokinetics

Katsuyoshi Matsuoka, Shunsuke Hamada, Mikiko Shimizu, Kosaku Nanki, Shinta Mizuno, Hiroki Kiyohara, Mari Arai, Shinya Sugimoto, Yasushi Iwao, Haruhiko Ogata, Tadakazu Hisamatsu, Makoto Nagauma, Takanori Kanai, Mayumi Mochizuki, Masayuki Hashiguchi

Research output: Contribution to journalArticle

Abstract

Objective: Crohn's disease (CD) is a chronic inflammatory gastrointestinal disease with repeated cycles of exacerbation and remission. Infliximab (IFX), a chimeric anti-TNF-α monoclonal antibody, has been widely used for the treatment of CD. However, no study in Japanese CD patients receiving continuous IFX for more than 1 year has been reported. To avoid therapeutic failure during long-term administration in Japanese CD patients, we evaluated the variable factors of IFX pharmacokinetics and the optimal trough IFX concentration at 8 weeks after administration. Materials and methods: Population pharmacokinetic (PPK) analysis was performed using the nonlinear mixed-effect model based on the IFX serum concentration in 832 samples from 121 patients. A one-compartment model was used to examine interindividual variability in the systemic clearance (CL) of intravenously administered IFX. Results: PPK estimates (estimated value, RSE%) were total clearance (CL: 0.018 L/h, 9.1) and volumes of distribution (Vd: 7.35 L, 12.0). Interindividual variability for CL and Vd of 0.11 and 0.16, respectively, was found. Body weight, antibody to IFX (ATI), and albumin level were factors affecting the IFX CL. IFX CL was greater in the ATI-positive than in the ATInegative group. CL was also greater in nonremission patients. There was a significant association between the predicted serum IFX trough concentration at 8 weeks and therapeutic response with long-term continuous administration (p < 0.05), with a higher concentration at 8 weeks seen in the remission group. Conclusion: Using these variables including body weight, ATI, and albumin level, the IFX dose could be calculated for individual CD patients to achieve the optimal therapeutic range.

Original languageEnglish
Pages (from-to)89-102
Number of pages14
JournalInternational journal of clinical pharmacology and therapeutics
Volume58
Issue number2
DOIs
Publication statusPublished - 2020

Keywords

  • Crohn's disease
  • Infliximab
  • Long-term therapeutic response
  • Pharmacodynamics
  • Population pharmacokinetics
  • Therapeutic concentration

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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