Effect kinetics of N-acetylprocainamide-induced QT interval prolongation.
We attempted to correlate clinical response with the effects of N-acetylprocainamide (NAPA) on the QT interval in five patients with stable chronic ventricular arrhythmias. A 15 mg/kg dose of NAPA was administered and a pharmacokinetic-pharmacodynamic model was used to relate plasma NAPA concentrations to changes in corrected QT interval (QTc). NAPA volume of distribution, elimination clearance, and elimination half-life averaged 1.37 +/- 0.19 L/kg, 174 +/- 63 ml/min, and 8.2 +/- 1.4 hours, respectively (mean +/- SD), and NAPA renal clearance averaged 1.9 +/- 0.6 times creatinine clearance. QTc prolongation was characterized by a linear-effect model in the first four patients and averaged 2.4 msec for every microgram per milliliter NAPA in a hypothetic biophase. QTc prolongation in patient 5 was exaggerated and was analyzed with an Emax model. Nonetheless, NAPA did not control this patient's arrhythmia. Conversely, patient 1 subsequently developed torsade de pointes even though QTc prolongation in this patient was comparable to that in patients 2 through 4, who responded satisfactorily to NAPA. We conclude that QT interval changes during initial NAPA administration do not reliably predict subsequent clinical response.
D000120:Acecainide / Q000097:blood / Q000378:metabolism* / Q000627:therapeutic use; D000368:Aged; D001145:Arrhythmias, Cardiac / Q000188:drug therapy / Q000378:metabolism*; D004562:Electrocardiography; D005260:Female; D006352:Heart Ventricles / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D011342:Procainamide / Q000031:analogs & derivatives*
D000120:Acecainide; D011342:Procainamide