Antazoline-insights into drug-induced electrocardiographic and hemodynamic effects: Results of the ELEPHANT II substudy.

Abstract

Antazoline is an old antihistaminic and new antiarrhythmic agent with unknown mechanisms of action which recently has been shown to effectively terminate atrial fibrillation. The aim of study was to examine the effects of antazoline on hemodynamic and ECG parameters. Antazoline was given intravenously in three 100mg boluses to 10 healthy volunteers (four males, mean age 40+11years). Hemodynamic and ECG parameters were measured using impedance cardiography [systolic (sBP), diastolic (dBP), mean (mBP) blood pressure, stroke volume (SV), cardiac output (CO), total peripheral resistance (TPR) and heart rate (HR), P wave, PR interval, QRS complex, QT and corrected QT (QTcF) interval]. Plasma concentration of antazoline was also measured. Antazoline caused significant prolongation of P wave, QRS as well as QT and QTcF (101±10 vs 110±16ms, p<.05, and 101±12 vs 107±12ms, p<.05, 399±27 vs 444±23ms, p<.05, and 403±21 vs 448±27ms, p<.05, respectively). Also, a significant decrease in SV was noted (94.9±21.8 vs 82.4±19.6 ml, p<.05). A significant correlation between changes in plasma drug concentration and changes in CO, HR, and dBP was found. Antazoline impairs slightly hemodynamics, significantly reducing SV. Significant prolongation of P wave and QRS duration corresponds to drug-induced prolongation of conduction, whereas QT prolongation represents drug-induced prolongation of repolarization.