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Effects of Antihistamins on the Cardiovascular System in Telemetered Conscious Dogs

Two Antihistamines, terfenadine and astemizole have been withdrawn from major markets for the reason that these durgs have been reported to induce QT interval prolongation associaed with the onset of Torsades de Pointes (TdP), resulting in a life-theatening ventricular arrhythmia. In this study, we investigated effects of diphenhydramine on electrocardigrans and hemodynamic parameters in conscious telemetered dogs. We validated and defined the sensitivity of the test system by monitoring basal parameters and using positive control substancem terfenadine. Single administration effects were tested during 24 hours for each test drug at dose 1㎎/㎏, 10㎎/㎏, 30㎎/㎏, 100㎎/㎏. We monitored QT, QTc, heart rate, blood pressure and body temperature after administering test drugs. In conscious telemetered dogs, diphenhydramine significantly prolonged QT (6.8% of basal) and (7.8% of basal) at 100㎎/㎏. Other parameters were not affected significantly. These findings suggest that antihistamines could induce inportant clinical relevance for patients taking excessive dosages of conventional antihistamines and those at risk of developing cardiac arrhythmias. Future studies that include other antihistamines and other classes will be necessary to predict the torsadogenic risk of drug in humans.