Comparative cardiac electrophysiologic study of PK 10139, a new antiarrhythmic agent, and quinidine in anesthetized dogs: plasma concentration-response relationships.
Cardiac electrophysiologic effects of PK 10139 (PK), a new quinoleic antiarrhythmic agent, were compared with those of quinidine sulphate (Q) after three cumulative intravenous doses of 0.75, 1.5, and 3 mg/kg of PK and 5, 10, and 20 mg/kg of Q in anesthetized dogs. A control group of animals received saline solution only. Both PK and Q provoked an increase, correlated with plasma concentrations, in atrionodal (St-H), His-Purkinje system (HV), and auriculoventricular (QS) conduction times, and auricular effective and functional refractory periods (AERP, AFRP). The effects of PK on conduction times were more marked than those of Q. Slopes of the plasma concentration-effect curves were similar for the two drugs for HV and QS but different for St-H. PK was 42.5 times more potent than Q in increasing HV and 46 times more potent than Q in increasing QS. Effects of PK on AFRP and nodal FRP did not differ from those observed in control animals. These findings demonstrate more marked effects of PK, when compared with Q, at doses 6.7 times lower and at plasma concentrations 15 to 42 times less, without chronotropic effects or significant alterations in blood pressure, and without adverse reactions on the central nervous system.
Heckle
J
J
Jaillon
P
P
Jozefczak
C
C
Cheymol
G
G
D000758:Anesthesia; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000097:blood / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D006321:Heart / Q000187:drug effects*; D006329:Heart Conduction System / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D011802:Quinidine / Q000097:blood / Q000494:pharmacology*; D011804:Quinolines / Q000097:blood / Q000494:pharmacology*; D012032:Refractory Period, Electrophysiological / Q000187:drug effects
D000889:Anti-Arrhythmia Agents; D011804:Quinolines; C037907:quinacainol; D011802:Quinidine