<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

Q: What is the clinical evidence from this study?

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.

Q: 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.

doi:10.34429/00002899

January 1, 2004Open Access

<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

View Full Paper

Ask AI

Bookmark

Share

Key result

Matsunaga and Van de Water formulas outperform Bazett and Fridericia for QT rate-correction in canines.

n=4

Why the study?

The study was conducted to assess the QT-prolonging effects of the histamine H1 receptor antagonist terfenadine and evaluate four mathematical methods for rate-correction of the QT interval.

Key Points

To assess the QT-prolonging effects of terfenadine and compare four mathematical rate-correction formulas for ventricular repolarization in an in vivo canine model.
In vivo electrophysiological and hemodynamic evaluation in halothane-anesthetized dogs (n=4).
Administered intravenous terfenadine at therapeutic (0.3 mg/kg) and supra-therapeutic (3 mg/kg) doses.
Measured surface ECG intervals, His bundle electrograms, and monophasic action potential duration (MAP90) during sinus rhythm and ventricular pacing (CL300 and CL400), evaluating Bazett, Fridericia, Van de Water, and Matsunaga correction formulas.
Terfenadine at 0.3 mg/kg prolonged the HV interval at 10, 20, and 30 min and increased Bazett-corrected QTc at 10 and 30 min without altering blood pressure or heart rate.
At 3 mg/kg, terfenadine transiently increased heart rate (5–10 min) and cardiac output (5–10 min), reduced mean blood pressure (5–30 min), and prolonged QRS width, ERP (5–60 min), MAP90(sinus) (20–60 min), and QTc calculated via all four formulas.
Correlation coefficients between MAP90(CL400) and corrected MAP90(sinus) were 0.900 ± 0.044 for Matsunaga, 0.898 ± 0.046 for Van de Water, 0.822 ± 0.091 for Fridericia, and 0.688 ± 0.14 for Bazett.

Structured PICO

P

Population

Halothane-anesthetized canine model (n=4)

I

Intervention

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

O

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

Implication

Hypothesis-generating for QT rate-correction in canine models; does not support changes to clinical QT assessment.

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.

Discussion

No takes yet. Share an insight, caveat, or question.

Cite This Study

A 2004 study studied Healthy (canine model) (n=4). Terfenadine vs. Pre-drug baseline was evaluated on Correlation coefficient between MAP90(CL400) and corrected MAP90(sinus) using Matsunaga's formula. 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.

synapsesocial.com/papers/6a1e72cb30b38c64201b60c8 https://doi.org/10.34429/00002899

View Full Paper

Ask AI

Bookmark

Share

<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

Key Points

Structured PICO

Limitations

Implication

Abstract

Discussion

Cite This Study

<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

Key Points

Structured PICO

Limitations

Implication

Abstract

Discussion

Cite This Study

Keep reading

More related papers

Keep reading

More related papers