山梨医科学雑誌　第19巻3号　089-099(2004)

＜Original Article＞
The QT-Prolonging Effects of a Histamine H1 Receptor Antagonist
Terfenadine Assessed in the In Vivo Canine Heart Model:
Comparison of the Rate-Correcting Methods
for the Ventricular Repolarization Periods

Akira TAKAHARA, Atsushi SUGIYAMA,
Yoshioki SATOH, and Keitaro HASHIMOTO

Abstract:　The QT-prolonging effects of the histamine H1 receptor antagonist terfenadine were assessed using the halothane-anesthetized canine model to evaluate four mathematical methods for rate-correction of the QT interval. Administration of a therapeutic dose of terfenadine (0.3 mg/kg, i.v., n ＝4) prolonged intraventricular conduction without affecting the other cardiovascular parameters. Additional administration of supra-therapeutic dose of terfenadine (3 mg/kg, i.v.) decreased the blood pressure as well as preload and afterload of the left ventricle, increased the heart rate and cardiac output, and prolonged the monophasic action potential duration (MAP90), effective refractory period and intraventricular conduction. The QTc obtained using FridericiaOs, Van de WaterOs and MatsunagaOs formulas was prolonged at 3 mg/kg while that obtained using BazettOs formula increased from 0.3 mg/kg. Correlation between the MAP90 during the sinus rhythm corrected by the formula of Van de Water or Matsunaga (cMAP90) versus MAP90(CL400) gave higher correlation coefficients than that corrected by BazettOs or FridericiaOs formulas. Therefore, MatsunagaOs and Van de WaterOs formulas would be better mathematical methods in comparison with BazettOs and FridericiaOs for the assessment of QT-prolonging drugs in dogs for preclinical studies.

Key words: terfenadine, monophasic action potential, QTc, Bazett, Van de Water



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