CANINE-EFFECTIVE PLASMA-CONCENTRATIONS OF ANTI-ARRHYTHMIC DRUGS ON THE 2-STAGE CORONARY LIGATION ARRHYTHMIA

Abstract

Seven drugs were tested for their antiarrhythmic effects on ventricular arrhythmias 24 and 48 h after 2-stage coronary ligation in conscious beagles. Venous blood samples were drawn for plasma drug assays. Minimum effective plasma concentrations of drugs were calculated from derived concentration-time curves. Effective drugs and their minimum effective concentrations for the suppression of arrhythmias 24 and 48 h after coronary ligation were disopyramide, 4.2 and 2.3 .mu.g/ml; procainamide, 26.4 and 27.0 .mu.g/ml; phenytoin, 8.4 and 6.4 .mu.g/ml; and a new .beta.-blocker, N-696 [4-[3(tert-butylamino)-2-hydroxypropoxy]-N-methylisocarbostyril], 7.6 and 8.7 .mu.g/ml. The concentrations of disopyramide and phenytoin were almost the same as those reported for human antiarrhythmic concentrations, but those of procainamide were higher than those reported for man. Lidocaine, verapamil and a new .beta.-blocker, OPC-1427 [bometolol], were ineffective. Membrane-stabilizing effects seem to be important in suppressing the canine 2-stage coronary ligation arrhythmia.