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Cardiovasc Toxicol (2015) 15:197202
DOI 10.1007/s12012-014-9285-8
Analysis of an ECG Record Database Reveals QT Interval Prolongation Potential of Famotidine in a Large Korean Population
Jaesuk Yun Eun Hwangbo Jongpill Lee Chong-Run Chon Peol A. Kim
In-Hye Jeong Manyoung Park Raewoong Park Shin-Jung Kang
Donwoong Choi
Published online: 25 September 2014 Springer Science+Business Media New York 2014
Abstract Some non-antiarrhythmic drugs have the undesirable property of delaying cardiac repolarization, an effect that can be measured empirically as a prolongation of the QT interval by surface electrocardiogram (ECG). The QT prolongation and proarrhythmia potential of famotidine are largely unknown, particularly in individuals that have cardiovascular risk factors such as abnormal electrolyte levels. Based on an analysis of QT/QTc intervals from a database of ECG recordings from a large Korean population (ECG-ViEW, 710,369 ECG recordings from 371,401 individuals), we observed that famotidine administration induced a prolonged QTc interval (above 480 ms, p \ 0.05 compared to before-treatment, based on a McNemar test). Furthermore, famotidine induced QT prolongations in 10 out of 14 patients with hypocalcemia and 11 out of 13 patients with hypomagnesemia [difference of mean between before and after famotidine administration; 38.00 ms (95 % condence interval 2.7273.28) and 67.08 ms (95 % condence interval24.94109.21), p \ 0.05 and p \ 0.01 by paired t test, respectively]. In vitro, the IC50 of famotidine for human-ether-a-go-go gene (hERG) channel inhibition was higher
than 100 lM as determined by automated patch clamp hERG current assay, implying that hERG channel inhibition is not the underlying mechanism for QT prolongation. These results suggest that famotidine administration increases a proar-rhythmic potential, especially in subjects with electrolytes imbalance.
Keywords QT prolongation Famotidine ECG-ViEW
Regulation hERG assay Korean population
Introduction
One undesirable property of certain non-antiarrhythmic drugs is that they can delay cardiac repolarization, which can be detected via surface electrocardiogram (ECG) as a prolongation of the QT interval [1]. The QT interval represents the duration of ventricular depolarization and subsequent repolarization, and it is measured from the beginning of the QRS complex to the end of the T wave. Prolongation of the QT interval is generally thought to be a biomarker for assessing the development of cardiac arrhythmias, including torsade de pointes (TdP) arrhythmias.
In the course of preclinical drug development, most development...