Yun Jaesuk, Hwangbo Eun, Lee Jongpill, Chon Chong-Run, Kim Peol A, Jeong In-Hye, Park Manyoung, Park Raewoong, Kang Shin-Jung, Choi Donwoong
Pharmaceutical Standardization Research and Testing Division, National Institute of Food and Drug Safety Evaluation (NIFDS), Ministry of Food and Drug Safety (MFDS), OHTAC 187, Osongsaengmyeong-2ro, Osong, Cheongju-si, Chungbuk, 363-700, Republic of Korea,
Cardiovasc Toxicol. 2015 Apr;15(2):197-202. doi: 10.1007/s12012-014-9285-8.
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.
一些非抗心律失常药物具有延迟心脏复极化的不良特性，这种效应可通过体表心电图（ECG）测量QT间期延长来实证评估。法莫替丁的QT间期延长和促心律失常潜力在很大程度上尚不清楚，尤其是在有心血管危险因素（如电解质水平异常）的个体中。基于对来自大量韩国人群的心电图记录数据库（ECG-ViEW，来自371,401名个体的710,369份心电图记录）中的QT/QTc间期分析，我们观察到给予法莫替丁会导致QTc间期延长（超过480毫秒，基于McNemar检验，与治疗前相比p<0.05）。此外，法莫替丁使14名低钙血症患者中的10名以及13名低镁血症患者中的11名出现QT延长[法莫替丁给药前后的平均差异；38.00毫秒（95%置信区间2.72 - 73.28）和67.08毫秒（95%置信区间24.94 - 109.21），配对t检验分别为p<0.05和p<0.01]。在体外，通过自动膜片钳hERG电流测定法确定，法莫替丁对人ether-a-go-go基因（hERG）通道抑制的IC50高于100μM，这意味着hERG通道抑制不是QT延长的潜在机制。这些结果表明，给予法莫替丁会增加促心律失常潜力，尤其是在电解质失衡的受试者中。
