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.
Doki
Kosuke
K
Department of Pharmaceutical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Ten-nodai 1-1-1, Tsukuba, Ibaraki, 305-8575, Japan.
Homma
Masato
M
Kuga
Keisuke
K
Aonuma
Kazutaka
K
Sakai
Satoshi
S
Yamaguchi
Iwao
I
Kohda
Yukinao
Y
D000328:Adult; D000368:Aged; D000889:Anti-Arrhythmia Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D044466:Asian People; D002851:Chromatography, High Pressure Liquid; D003430:Cross-Sectional Studies; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics / Q000378:metabolism; D015716:Electrocardiography, Ambulatory; D005260:Female; D005424:Flecainide / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D062554:NAV1.5 Voltage-Gated Sodium Channel; D011401:Promoter Regions, Genetic; D012737:Sex Factors; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism; D013617:Tachycardia, Supraventricular / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D013997:Time Factors; D016896:Treatment Outcome
D000889:Anti-Arrhythmia Agents; D009124:Muscle Proteins; D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human; D015222:Sodium Channels; D019389:Cytochrome P-450 CYP2D6; D005424:Flecainide