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Analysis of an ECG Record Database Reveals QT Interval Prolongation Potential of Famotidine in a Large Korean Population

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 % confidence interval 2.72–73.28) and 67.08 ms (95 % confidence interval 24.94–109.21), 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 μM 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 proarrhythmic potential, especially in subjects with electrolytes imbalance.

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Acknowledgments

This study was supported by 13171MFDS224 by Ministry of Food and Drug Safety, Republic of Korea.

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The authors declare no conflict of interest.

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Correspondence to Jaesuk Yun.

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Jaesuk Yun and Eun Hwangbo have contributed equally to this work.

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Yun, J., Hwangbo, E., Lee, J. et al. Analysis of an ECG Record Database Reveals QT Interval Prolongation Potential of Famotidine in a Large Korean Population. Cardiovasc Toxicol 15, 197–202 (2015). https://doi.org/10.1007/s12012-014-9285-8

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Keywords

  • QT prolongation
  • Famotidine
  • ECG-ViEW
  • Regulation
  • hERG assay
  • Korean population