The influence of CYP2D6 polymorphism on the antiarrhythmic efficacy of propafenone in patients with paroxysmal atrial fibrillation during 3 months propafenone prophylactic treatment

Objective: Propafenone (PPF) is an antiarrhythmic, Class Ic agent. Its meta bolism is genetically controlled by a cytochrome P450 isoenzyme named CYP2D 6, which shows polymorphism in human population. The aim of this paper was to determine the correlation between the antiarrhythmic efficacy of PPF and the oxidation phenotype. Subjects and material: The study group consisted of 42 patients, aged 36 to 75 years, suffering from paroxysmal atrial fibri llation (AF). The oxidation phenotype was described by the metabolic ratio (MR) of sparteine. The MR value separated the group of poor metabolizers (M R > 20) from the group of extensive metabolizers (MR < 20) with the subgrou p of very extensive metabolizers (MR < 1). Method: The study was conducted during a 3-month PPF therapy for the prophylaxis of paroxysmal atrial fibri llation. PPF was given orally, 300 - 450 mg/day. The oxidation phenotype wa s checked prior to the administration of PPF. Serum concentration of PPF at 7, 11 days and the end of PPF therapy were determined. Statistical analysi s of data was performed with the chi (2) test and the Pearson's correlation methods. Results: In the group of 42 patients, PPF therapy was 100% effect ive in poor metabolizers (PM). In extensive metabolizers (EM), 61% efficacy was observed with efficacy 0% in very extensive metabolizers (VEM). The co rrelation between oxidation phenotype and the ability to maintain sinus rhy thm (SR) was statistically significant (r = 0.414, p < 0.05). Conclusions: The antiarrhythmic efficacy of propafenone depends on the oxidation phenoty pe; 100% efficacy occurred in the group of poor metabolizers whereas PPF, a t the dose tested, was ineffective in very extensive metabolizers.