Sustained QT prolongation induced by tacrolimus in guinea pigs

Tsuyoshi Minematsu, Hisakazu Ohtani, Hitoshi Sato, Tatsuji Iga

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Recently, clinical cases have been reported of QT prolongation and torsades de pointes associated with the use of tacrolimus (FK506). We examined the relationship between QTc prolongation and the pharmacokinetics of FK506 in guinea pigs in order to evaluate the arrhythmogenicity of FK506 in comparison with quinidine (QND). FK506 (0.1 or 0.01 mg/hr/kg) or QND (30 mg/hr/kg) was intravenously infused to guinea pigs and time profiles of drug concentration in blood and QTc interval were examined during and after infusion. Both FK506 and QND evoked a significant QTc prolongation, and the dose-response relationship showed an anti-clockwise hysteresis, FK506-induced QTc prolongation persisted throughout the duration of the experiment despite a decline in the plasma FK506 concentration, whilst QND-induced QTc prolongation disappeared as plasma concentrations decreased. FK506 induced a sustained QTc prolongation in guinea pigs at drug concentrations in blood that correspond to its therapeutic range in human, suggesting that it might be of clinical significance to monitor the electrocardiogram, especially when patients have congenital or acquired QT-prolonging risk factors.

Original languageEnglish
Pages (from-to)PL197-PL202
JournalLife Sciences
Volume65
Issue number14
DOIs
Publication statusPublished - 1999 Aug 27
Externally publishedYes

Keywords

  • Arrhythmia
  • Electrocardiogram
  • Guinea pig
  • QT prolongation
  • Quinidine
  • Tacrolimus

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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