Nonlinear mixed effects model analysis of the pharmacokinetics of routinely administered bepridil in Japanese patients with arrhythmias

Masato Taguchi, Akira Fujiki, Jotaro Iwamoto, Hiroshi Inoue, Katsutoshi Tahara, Katsuya Saigusa, Isao Horiuchi, Yukari Oshima, Yukiya Hashimoto*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

This study was performed to evaluate variability in the pharmacokinetics of bepridil in 38 Japanese patients with arrhythmias, and to investigate the effects of aprindine as well as CYP2D6 and CYP3A5 polymorphisms on the oral clearance of bepridil. We determined the polymorphic alleles of CYP2D6 and CYP3A5 in each subject. The plasma concentration of bepridil at steady-state following repetitive oral administration was measured with an HPLC-based method, and the oral clearance was estimated using the nonlinear mixed effects model (NONMEM) program. Mean oral clearance was significantly greater in the patients with the CYP2D6*10 allele than in those without it. On the other hand, no significant effect of the CYP3A5 polymorphism was observed on the pharmacokinetics of bepridil. In addition, aprindine seemed to reduce the oral clearance of bepridil in the patients with the CYP2D6*10 allele.

Original languageEnglish
Pages (from-to)517-521
Number of pages5
JournalBiological and Pharmaceutical Bulletin
Volume29
Issue number3
DOIs
StatePublished - 2006/03

Keywords

  • Aprindine
  • Bepridil
  • CYP2D6*10
  • Nonlinear mixed effects model
  • Pharmacokinetics

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

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