What is the clinical evidence from this study?

Study design: Other. Population: Healthy (canine model) (n=4). Intervention: Terfenadine vs. Pre-drug baseline. Primary outcome: Correlation coefficient between MAP90(CL400) and corrected MAP90(sinus) using Matsunaga's formula.

What does this research mean for the field?

Matsunaga's and Van de Water's formulas provide more accurate rate-correction for the QT interval than Bazett's and Fridericia's formulas when assessing QT-prolonging drugs in preclinical canine models. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

This study aims to evaluate the QT-prolonging effects of terfenadine and compare rate-correction methods for the QT interval.

June 2, 2026Open Access

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

Key Result

Matsunaga's and Van de Water's formulas provided better rate-correction of the QT interval (correlation coefficients 0.900 and 0.898) than Bazett's and Fridericia's formulas in a canine model.

Key Points

This study aims to evaluate the QT-prolonging effects of terfenadine and compare rate-correction methods for the QT interval.
Used halothane-anesthetized canine model
Administered therapeutic (0.3 mg/kg) and supra-therapeutic (3 mg/kg) doses of terfenadine
Assessed four mathematical methods for QT interval rate-correction
QTc prolonged with terfenadine 3 mg/kg using Fridericia and Matsunaga formulas.
Matsunaga and Van de Water formulas showed higher correlation coefficients with MAP90 compared to Bazett and Fridericia formulas.
Administration of 3 mg/kg terfenadine decreased blood pressure and affected left ventricular parameters.

Structured PICO

Population

Halothane-anesthetized canine model (n=4)

Intervention

Terfenadine (0.3 mg/kg i.v. therapeutic dose, followed by 3 mg/kg i.v. supra-therapeutic dose)

Outcome

QT interval prolongation and evaluation of four mathematical methods for rate-correction of the QT interval (Bazett, Fridericia, Van de Water, Matsunaga)surrogate

Matsunaga's and Van de Water's formulas are superior to Bazett's and Fridericia's for assessing QT-prolonging drugs in preclinical canine studies.

Limitations

Small sample size (n=4)
Animal model (dogs) may not perfectly translate to humans
Use of halothane anesthesia may affect cardiovascular parameters

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.

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