[Pharmacokinetics of oral propafenone in patients with supraventricular arrhythmia]

The efficacy of propafenone (P), a class IC antiarrhythmic drug with weak beta-blocking properties was studied over a four day period in 10 patients with supraventricular arrhythmias (atrial fibrillation 7, flutter 1 and tachycardia 2). Group 1 included five patients (3M, 2F) who received 300 mg of P on days 1 and 4. Group 2 included five patients (4M, 1F) who received 600 mg on days 1 and 4. All the patients received 1200 mg/day on days 2 and 3. Pharmacokinetics parameters were calculated for the first and the final dosing. Half of the patients were converted to sinus rythm after a delay ranging from 12 to 55 h after the first dosing. The duration of arrhythmia was shorter and the left atrial diameter was significantly lower in the responder group than in the non-responders. No relationship was observed between clinical efficacy and dose or plasma concentration of P. After the first administration of P, major interindividual variability in pharmacokinetic parameters was observed. Seven patients correspond to the extensive metabolizer phenotype with t1/2 el less than 10 h (mean: 5.4 +/- 2.2 SD). In this group t1/2 el increased from day 1 to day 4 and the AUC final/AUC initial ratio ranged between 4 to 17.5. Three patients showed the non-extensive metabolizer phenotype with t1/2 el ranging from 12.4 to 13.7 h and a moderate increase in AUC over chronic dosing. Adverse effects (cardiac conduction abnormalities, visual and digestive disturbances) were observed in the 3 oldest patients (70-73 yrs).(ABSTRACT TRUNCATED AT 250 WORDS)