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Start Over Author "Florian, Jeff" Topic anti-arrhythmia agents
2 results on '"Florian, Jeff"'

1. Are women more susceptible than men to drug-induced QT prolongation? Concentration-QTc modelling in a phase 1 study with oral rac-sotalol.

Author

Darpo B, Karnad DR, Badilini F, Florian J, Garnett CE, Kothari S, Panicker GK, and Sarapa N

Subjects
Administration, Oral, Adrenergic beta-Antagonists administration & dosage, Adrenergic beta-Antagonists pharmacokinetics, Anti-Arrhythmia Agents administration & dosage, Anti-Arrhythmia Agents pharmacokinetics, Drug Administration Schedule, Electrocardiography, Female, Humans, Linear Models, Long QT Syndrome diagnosis, Long QT Syndrome physiopathology, Male, Risk Assessment, Risk Factors, Sex Factors, Sotalol administration & dosage, Sotalol pharmacokinetics, Adrenergic beta-Antagonists adverse effects, Anti-Arrhythmia Agents adverse effects, Heart Rate drug effects, Long QT Syndrome chemically induced, Sotalol adverse effects
Abstract

Aim: To study the differences in QTc interval on ECG in response to a single oral dose of rac-sotalol in men and women., Methods: Continuous 12-lead ECGs were recorded in 28 men and 11 women on a separate baseline day and following a single oral dose of 160 mg rac-sotalol on the following day. ECGs were extracted at prespecified time points and upsampled to 1000 Hz and analyzed manually in a central ECG laboratory on the superimposed median beat. Concentration-QTc analyses were performed using a linear mixed effects model., Results: Rac-sotalol produced a significant reduction in heart rate in men and in women. An individual correction method (QTc I) most effectively removed the heart rate dependency of the QTc interval. Mean QTc I was 10 to 15 ms longer in women at all time points on the baseline day. Rac-sotalol significantly prolonged QTc I in both genders. The largest mean change in QTc I (ΔQTc I) was greater in females (68 ms (95% confidence interval (CI) 59, 76 ms) vs. 27 ms (95% CI 22, 32 ms) in males). Peak rac-sotalol plasma concentration was higher in women than in men (mean Cmax 1.8 μg ml(-1) (range 1.1-2.8) vs. 1.4 μg ml(-1) (range 0.9-1.9), P = 0.0009). The slope of the concentration-ΔQTc I relationship was steeper in women (30 ms per μg ml(-1) vs. 23 ms per μg ml(-1) in men; P = 0.0135)., Conclusions: The study provides evidence for a greater intrinsic sensitivity to rac-sotalol in women than in men for drug-induced delay in cardiac repolarization., (© 2013 The British Pharmacological Society.)

Published
2014
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2. Are women more susceptible than men to drug-induced QT prolongation? Concentration-QTc modelling in a phase 1 study with oral rac-sotalol

Author

Darpo, Borje, Karnad, Dilip R, Badilini, Fabio, Florian, Jeff, Garnett, Christine E, Kothari, Snehal, Panicker, Gopi Krishna, and Sarapa, Nenad

Subjects
Male, Pharmacokinetic Dynamic Relationships, Adrenergic beta-Antagonists, Sotalol, Administration, Oral, Risk Assessment, Drug Administration Schedule, Electrocardiography, Long QT Syndrome, Sex Factors, Heart Rate, Risk Factors, Linear Models, Humans, Female, Anti-Arrhythmia Agents
Abstract

To study the differences in QTc interval on ECG in response to a single oral dose of rac-sotalol in men and women.Continuous 12-lead ECGs were recorded in 28 men and 11 women on a separate baseline day and following a single oral dose of 160 mg rac-sotalol on the following day. ECGs were extracted at prespecified time points and upsampled to 1000 Hz and analyzed manually in a central ECG laboratory on the superimposed median beat. Concentration-QTc analyses were performed using a linear mixed effects model.Rac-sotalol produced a significant reduction in heart rate in men and in women. An individual correction method (QTc I) most effectively removed the heart rate dependency of the QTc interval. Mean QTc I was 10 to 15 ms longer in women at all time points on the baseline day. Rac-sotalol significantly prolonged QTc I in both genders. The largest mean change in QTc I (ΔQTc I) was greater in females (68 ms (95% confidence interval (CI) 59, 76 ms) vs. 27 ms (95% CI 22, 32 ms) in males). Peak rac-sotalol plasma concentration was higher in women than in men (mean Cmax 1.8 μg ml(-1) (range 1.1-2.8) vs. 1.4 μg ml(-1) (range 0.9-1.9), P = 0.0009). The slope of the concentration-ΔQTc I relationship was steeper in women (30 ms per μg ml(-1) vs. 23 ms per μg ml(-1) in men; P = 0.0135).The study provides evidence for a greater intrinsic sensitivity to rac-sotalol in women than in men for drug-induced delay in cardiac repolarization.

Published
2014

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