A comparative pharmacodynamic study of the arrhythmogenicity of antidepressants, fluvoxamine and imipramine, in guinea pigs

Hisakazu Ohtani, Y. Odagiri, H. Sato, Y. Sawada, T. Iga

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Among several classes of antidepressants, tricyclic antidepressants are known to prolong QTc intervals (QT interval corrected by heart rate) in electrocardiograms, while selective serotonin uptake inhibitors (SSRI) are considered to be devoid of arrhythmogenicity. In this study, we aimed to compare the arrhythmogenic potencies of imipramine (IMI), a typical tricyclic antidepressant, and fluvoxamine (FLV), an SSRI, at therapeutic and supratherapeutic concentrations using guinea pigs in vivo. Guinea pigs were anesthetized, and IMI (10 and 20 mg/kg/h) or FLV (20 mg/kg/h) was intravenously administered for 90 minutes to obtain the time-courses of drug concentrations in plasma and the changes in the QTc intervals during and after the drug administration. IMI induced distinct QTc prolongation in a dose-dependent manner, while FLV prolonged QTc intervals only slightly. A pharmacokinetic-pharmacodynamic analysis revealed that the potency for QTc prolongation of IMI was 1.7-fold higher than that of FLV. Taking the therapeutic concentration into account, the clinical risk of FLV for QTc prolongation was suggested to be 5-fold lower than that of IMI. Therefore, this SSRI agent was suggested to be safer than the tricyclic antidepressant for patients with cardiac risk factors, including arrhythmia, or for those taking other arrhythmogenic drugs concomitantly.

Original languageEnglish
Pages (from-to)550-554
Number of pages5
JournalBiological and Pharmaceutical Bulletin
Volume24
Issue number5
DOIs
Publication statusPublished - 2001
Externally publishedYes

Fingerprint

Fluvoxamine
Imipramine
Antidepressive Agents
Guinea Pigs
Tricyclic Antidepressive Agents
Serotonin Uptake Inhibitors
Pharmaceutical Preparations
Cardiac Arrhythmias
Electrocardiography
Pharmacokinetics
Heart Rate
Therapeutics

Keywords

  • Arrhythmia
  • Fluvoxamine
  • Imipramine
  • QT interval

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

A comparative pharmacodynamic study of the arrhythmogenicity of antidepressants, fluvoxamine and imipramine, in guinea pigs. / Ohtani, Hisakazu; Odagiri, Y.; Sato, H.; Sawada, Y.; Iga, T.

In: Biological and Pharmaceutical Bulletin, Vol. 24, No. 5, 2001, p. 550-554.

Research output: Contribution to journalArticle

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