We prospectively evaluated reaching of steady state and clinical efficacy of propafenone (PPF), class Ic antiarrhythmic agent, in 16 patients (pts) (age 46-69, mean 57 years) with symptomatic ventricular arrhythmias (Low class II and IV). The majority (13 pts) had coronary artery disease. Drug was administered for 7 days (daily dose: 3 x 150 mg). Efficacy was defined as > 80% reduction of ventricular premature complexes (VPC) and class IV elimination in 24-hours Holter recording. Responders were continued on PPF for 3 weeks, in non-responders dose was titrated to 900 mg a day for the next 7 days. After second Holter evaluation the treatment was continued for 2 weeks in responders group. The non-responders were switched to other drug. After 4 weeks final Holter monitoring was performed. Serum concentration of PPF and its 2 metabolites: 5-hydroxy PPF and N-depropyl PPF were determined in 2, 3, 4, 5, 6, 7th day, just before the morning dose (3 x 150 mg/day) in 9 pts.
Results: Trough serum concentrations of PPF differed in high degree: 0-226 ng/ml (2nd day), 22-438 ng/ml (4th day), 42-614 ng/ml (6-7 day). An increasing tendency of serum concentrations of PPF was observed, so steady-state was not reached. This great dispersion of concentration values is because of non-linear metabolism and individual differences. Defined efficacy critetion was achieved in 62% pts, 56% for lower dose. Mean frequency of VPC was reduced by 86% in 24-hour Holter recording and per hour (p = 0.0011). Reduction of couplets/24 h was 87% (p = 0.0175). Significant prolongation of PQ (14%, p = 0.009) and QRS (13%, p = 0.0052) were observed. Changes of QT interval were not significant. One case of proarrhythmia was the cause of stopping the treatment.
Conclusions: Serum concentrations' values undermine common opinion, that steady state can be reached after 1-2 days of treatment. High dispersion of serum levels is the result of nonlinear metabolism of PPF and individual differences. In spite of this the study showed defined antiarrhythmic efficacy in 62.5% pts. In this group 90% success rate was achieved after lower dose 3 x 150 mg.