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.
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.
Authors: B Houltz; B Darpö; N Edvardsson; P Blomström; J Brachmann; H J Crijns; S M Jensen; E Svernhage; H Vallin; K Swedberg Journal: Pacing Clin Electrophysiol Date: 1998-05 Impact factor: 1.976
Authors: V Gotta; F Cools; K van Ammel; D J Gallacher; S A G Visser; F Sannajust; P Morissette; M Danhof; P H van der Graaf Journal: Br J Pharmacol Date: 2015-07-21 Impact factor: 8.739
Authors: Josée Bouchard; Greene Shepherd; Robert S Hoffman; Sophie Gosselin; Darren M Roberts; Yi Li; Thomas D Nolin; Valéry Lavergne; Marc Ghannoum Journal: Crit Care Date: 2021-06-10 Impact factor: 9.097