Effect kinetics of N-acetylprocainamide-induced QT interval prolongation

• Published in: Clinical pharmacology and therapeutics Vol. 42; no. 1; p. 107
• Main Authors: Piergies, A A, Ruo, T I, Jansyn, E M, Belknap, S M, Atkinson, Jr, A J
• Format: Journal Article
• Language: English
• Published: United States 01.07.1987
• Subjects: Acecainide - blood; Acecainide - metabolism; Acecainide - therapeutic use; Aged; Arrhythmias, Cardiac - drug therapy; Arrhythmias, Cardiac - metabolism; Electrocardiography; Female; Heart Ventricles - drug effects; Humans; Kinetics; Male; Middle Aged; Procainamide - analogs & derivatives
• ISSN: 0009-9236
• DOI: 10.1038/clpt.1987.117

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.