Clinical pharmacology and antiarrhythmic efficacy of N-acetylprocainamide.
Eleven patients with chronic ventricular arrhythmias took part in a study of N-acetylprocainamide (NAPA), the major metabolite of procainamide, in order to characterize further NAPA's clinical pharmacology and antiarrhythmic action. The frequency of ventricular arrhythmia on 24 hour ambulatory electrocardiographic recordings was comparable on recordings obtained in a prestudy screening, during treatment with placebo before administration of NAPA and after treatment with NAPA. The initial dosage of NAPA was 500 mg every 8 hours, which was increased by 500 mg increments every few days until 90 percent suppression of arrhythmia or intolerable adverse effects occurred. Only two patients achieved 90 percent suppression of ventricular ectopic complexes. The mean plasma concentration associated with 90 percent suppression of arrhythmia in these two patients ws 12.6 and 32.3 mg/ml, respectively. One of these two patients was unable to continue long-term therapy with NAPA because of a rash. Other adverse effects included gastrointestinal symptoms in seven patients with visual symptoms in four patients at plasma concentratons as low as 6.9 mg/ml. NAPA obeyed linear pharmacokinetics over the range of dosages studied (500 to 2,500 mg every 8 hours) and had a half-life of 10.7 +/- 1.98 hours (mean +/- standard deviation). There was no change in the P-R or QRS intervals and there was a dose-dependent prolongation of the Q-Tc interval. It is concluded that in this patient group, NAPA suppressed chronic ventricular ectopic complexes without adverse effects in only a minority of patients.
D000120:Acecainide / Q000097:blood / Q000378:metabolism* / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D001145:Arrhythmias, Cardiac / Q000188:drug therapy*; D003327:Coronary Disease / Q000401:mortality; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D005128:Eye Diseases / Q000209:etiology; D005260:Female; D005767:Gastrointestinal Diseases / Q000209:etiology; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D011342:Procainamide / Q000031:analogs & derivatives*; D014581:Urticaria / Q000209:etiology
D000120:Acecainide; D011342:Procainamide