Gender-associated differences in pharmacokinetics and anti-arrhythmic effects of flecainide in Japanese patients with supraventricular tachyarrhythmia.

Objective: We examined the effect of gender-associated differences in pharmacokinetics on the anti-arrhythmic effects of flecainide in Japanese patients with supraventricular tachyarrhythmia and in healthy subjects.

Methods: The study population comprised 72 outpatients (52 males and 20 females) treated with oral flecainide for supraventricular tachyarrhythmias. Serum flecainide concentrations were determined by use of high-performance liquid chromatography. The anti-arrhythmic efficacy of flecainide was assessed for at least 2 months through evaluation of symptomatology, electrocardiograms, and Holter monitoring. Pharmacokinetics of flecainide after a single 50-mg dose was examined in 14 healthy subjects (7 males and 7 females).

Results: The daily dose of flecainide did not differ between males and females (2.87 +/- 0.68 versus 2.92 +/- 0.90 mg/kg). The serum flecainide concentration was significantly lower in males than in females (315 +/- 151 versus 408 +/- 184 ng/mL, P < 0.05). Clinically relevant efficacy of flecainide was achieved significantly (P < 0.05) less often in male patients (31 of 52; 60%) than in female patients (19 of 20; 95%). We confirmed that nonrenal clearance of flecainide among healthy subjects was significantly higher in males than in females (0.77 +/- 0.16 versus 0.57 +/- 0.06 L h(-1) kg(-1), P < 0.05).

Conclusions: Our results suggest that the anti-arrhythmic efficacy of flecainide differed between males and females because of gender-associated differences in pharmacokinetics.