Pharmacokinetic - pharmacodynamic analysis of the arrhythmogenic potency of a novel antiallergic agent, ebastine, in rats

Hisakazu Ohtani, Hitoshi Sato, Tatsuji Iga, Hajime Kotaki, Yasufumi Sawada

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Ebastine (EBS), a novel nonsedative antiallergic agent, is similar to terfenadine in its chemical structure. However, clinical arrhythmogenicity of EBS remains controversial. In this study, we evaluated the possible arrhythmogenic potency of EBS as assessed by QT prolongation from a pharmacokinetic-pharmacodynamic viewpoint in comparison with that of terfenadine. EBS was intravenously infused into anesthetized rats at a rate of 3.0 or 10 mg/kg/h for 60 min, and electrocardiographic effects were continuously monitored from lead II. The plasma concentrations of EBS and its major metabolite, carebastine, were also measured under the same conditions. When intravenously administered, EBS exhibited QT prolongation in an infusion rate-dependent manner, with a lag time. Pharmacokinetic-pharmacodynamic analysis of EBS based on the effect-compartment model revealed values of EC50, E(max) and EC10 (ms) (where 10 ms of QT prolongation was evoked) of 0.73 μg/ml, 12.5 ms and 2.90 μg/mL, respectively. The EC(10 ms) value of EBS was five times higher than that of terfenadine reported previously In conclusion, EBS was suggested to be less arrhythmogenic than terfenadine.

Original languageEnglish
Pages (from-to)101-106
Number of pages6
JournalBiopharmaceutics and Drug Disposition
Volume20
Issue number2
DOIs
Publication statusPublished - 1999 Feb 23
Externally publishedYes

Keywords

  • Arrhythmia
  • ECG
  • Ebastine
  • Pharmacodynamics
  • Terfenadine

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science
  • Pharmacology (medical)

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