Comparison of Electrophysiological Effects of Quinidine and Hydroquinidine in Anesthetized Dogs

Cross‐over infusions of quinidine (Q) and hydrvcjuinidine (HQ) ivere perfonned at 8‐day intenmls in 12 pentobarhital‐anesthetized dogs. Three increasing doses were administered each time and the mean plasma concentrations (mg/L) were 2.8, 3.7, and 4.9 with Q and 1.2, 1.9, and 2.8 with HQ. Four electrophysiological studies were perfonned at baseline and after each dose. Both drugs exhibited Class IA effects without qualitative differences: sinus automaticiti/ and nodal conduction parameters were increased only Zi'ith the highest doses of drugs; His Purkinje (HV) and intraventricular (QRS) conduction times were increased consistently but only slightly and, for example, mean values of HV increased from 28 to 33 msec after Q and 30 to 34 msec after HQ. The largest increases were seen for QT interval (227 to 294 msec after Q and 237 to 292 msec after HQ), ventricular effective refractory periods (158 to 182 msec after Q and 161 to 185 msec after HQ), and atrial refractory periods (124 to 178 msec after Q and 120 to 172 msec after HQ). For the later parameter, hydroquinidine appeared significantly more potent with a potenaj ratio relative to quinidine estimated at 1.9 and 2.9 respectively for effective and functional atrial refractory periods. If confirmed, this higher potency of hydroquinidine versus quinidine should be clinicalli/ considered, for example, during drug plasma levels monitoring.