Pharmacodynamics of procainamide in patients with ventricular tachyarrhythmias.

Abstract

The onset and offset of the electropharmacologic effect of procainamide was studied in nine patients with ventricular arrhythmias. Procainamide was given at a constant infusion rate of 0.27 +/- 0.05 mg/kg/min for 50 to 60 minutes to an average total dose of 15.5 +/- 4.4 mg/kg. The QRS interval (used as an index of electropharmacologic effect) at a paced cycle length of 500 ms, and the plasma procainamide concentration were measured simultaneously every 5 minutes during infusion and at frequent intervals for up to 4 hours during a washout period. The average peak plasma concentration was 15.8 +/- 9.6 micrograms/ml and the average maximum QRS interval prolongation was 23.9 +/- 6.8% from baseline. The temporal and static plasma concentration-effect relationships were evaluated by pharmacodynamic modeling and linear regression. For six patients, there was a minimal (less than 2 minutes) delay in the plasma concentration-effect relationship, and the data fit a linear relationship with an average slope of 3.2 +/- 1.1 msec/microgram/ml. For the other three patients, there was a significant delay (3, 10, and 18 minutes respectively) in the plasma concentration-effect relationship. In most patients, the electropharmacologic effect of procainamide is rapid and proportional to plasma concentration; but in a minority of patients, significant delay occurs and could influence the results and interpretation of electropharmacologic studies.