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

  • Pharmacokinetics and Disposition
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European Journal of Clinical Pharmacology Aims and scope Submit manuscript

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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Acknowledgements

We greatly appreciate Eisai Co. Ltd. for providing flecainide acetate, MODF, MODLF and the internal standard for the assay. We acknowledge Mr. Y. Suzuki, Ms. K. Katori, Ms. T. Edo, Mr. T. Kawata, Ms. S. Shimada, and Ms. H. Ohata for their technical advice and assistance. This study complies with the current laws of Japan, where it was performed with ethics approval.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Ten-nodai 1-1-1, Tsukuba, Ibaraki, 305-8575, Japan

    Kosuke Doki, Masato Homma & Yukinao Kohda

  2. Department of Internal Medicine, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Ten-nodai 1-1-1, Tsukuba, Ibaraki, 305-8575, Japan

    Keisuke Kuga, Kazutaka Aonuma, Satoshi Sakai & Iwao Yamaguchi

Authors
  1. Kosuke Doki
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  2. Masato Homma
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  3. Keisuke Kuga
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  4. Kazutaka Aonuma
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  5. Satoshi Sakai
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  6. Iwao Yamaguchi
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  7. Yukinao Kohda
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Correspondence to Masato Homma.

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Doki, K., Homma, M., Kuga, K. et al. Gender-associated differences in pharmacokinetics and anti-arrhythmic effects of flecainide in Japanese patients with supraventricular tachyarrhythmia. Eur J Clin Pharmacol 63, 951–957 (2007). https://doi.org/10.1007/s00228-007-0348-7

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  • DOI: https://doi.org/10.1007/s00228-007-0348-7

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