Gender-associated differences in pharmacokinetics and anti-arrhythmic effects of flecainide in Japanese patients with supraventricular tachyarrhythmia |
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Authors: | Kosuke Doki Masato Homma Keisuke Kuga Kazutaka Aonuma Satoshi Sakai Iwao Yamaguchi Yukinao Kohda |
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Institution: | (1) Department of Pharmaceutical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Ten-nodai 1-1-1, Tsukuba, Ibaraki 305-8575, Japan;(2) Department of Internal Medicine, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Ten-nodai 1-1-1, Tsukuba, Ibaraki 305-8575, Japan |
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Abstract: | 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. |
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Keywords: | Flecainide Gender-associated difference Pharmacokinetics Anti-arrhythmic efficacy CYP2D6 |
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