The effect of a new inotropic agent, DPI 201-106, on systolic time intervals and the electrocardiogram in healthy subjects.
1. DPI 201-106 (DPI) is a novel inotropic agent, with Na+ channel agonistic action combined with a sensitization of contractile proteins to Ca++. In a double-blind trial in healthy volunteers (n = 20) cardiovascular effects (blood pressure, heart rate, ECG) of single oral doses were studied. In addition systolic time intervals (STIs) were assessed in 10 of these subjects. DPI plasma concentrations were measured by h.p.l.c. 2. Preejection period was shortened by 14 ms (P less than 0.01) and 30 ms (P less than 0.01) 1 h after 30 and 60 mg, respectively, suggesting a dose-dependent inotropic effect. Heart rate was slightly reduced after both doses. Mean blood pressure remained unchanged. 3. Corrected QT interval duration (QTc) was prolonged by a mean of 7 ms (NS) and 22 ms (P less than 0.001) 1 h after 30 and 60 mg, respectively. PQ and QRS intervals remained unaffected. 4. Peak plasma levels were attained at 1-2 h and the terminal elimination half-life was approximately 15 h. 5. It is concluded that DPI has positive inotropic and negative chronotropic properties which make it potentially useful for the treatment of heart failure.
Clinical Research Department, Sandoz Ltd, Basel, Switzerland.
P C
PC
Rüegg
E
E
Nüesch
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004562:Electrocardiography; D006339:Heart Rate / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D010879:Piperazines / Q000493:pharmacokinetics / Q000494:pharmacology*; D011897:Random Allocation
D010879:Piperazines; C046261:DPI 201-106