title: SCN5A promoter haplotype affects the therapeutic range for serum flecainide concentration in Asian patients.
abstract: OBJECTIVE
  An increased slowing of cardiac conduction induced by sodium channel blockers is remarkably observed in carriers of an Asian-specific promoter haplotype [haplotype B (HapB)] of the cardiac sodium channel gene (SCN5A). We investigated the effect of HapB on the therapeutic range for serum flecainide concentration in Asian patients.
  
  
  METHODS
  We examined the serum concentration and antiarrhythmic efficacy of flecainide, together with the SCN5A promoter haplotype, in 146 patients with supraventricular tachyarrhythmias. Trough serum flecainide concentrations were determined by HPLC. The antiarrhythmic efficacy of flecainide was assessed for at least 2 months through examination of symptomatology, ECG, and Holter monitoring.
  
  
  RESULTS
  The serum flecainide concentration did not differ between the wild-type HapA homozygotes and HapB carriers under treatment with the usual dose. A genetic difference in the antiarrhythmic efficacy of flecainide was observed between the HapA homozygotes and HapB carriers at serum flecainide concentrations less than 300 ng/ml (42.9 vs. 68.8%; P=0.022). PR prolongation and QRS widening were observed more commonly among the HapB carriers with serum flecainide concentrations of at least 300 ng/ml than in the HapA homozygotes (PR, 210 ± 25 vs. 195 ± 25 ms; P=0.036; and QRS, 112 ± 10 vs. 105 ± 9 ms; P=0.030).
  
  
  CONCLUSIONS
  These findings suggest that the therapeutic range for serum flecainide concentration is lower in HapB carriers than in HapA homozygotes.
authors: Department of Pharmaceutical Sciences, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.
authors: Kosuke
authors: K
authors: Doki
authors: Masato
authors: M
authors: Homma
authors: Keisuke
authors: K
authors: Kuga
authors: Kazutaka
authors: K
authors: Aonuma
authors: Yukinao
authors: Y
authors: Kohda
mesh_terms: D000368:Aged; D000889:Anti-Arrhythmia Agents / Q000097:blood* / Q000494:pharmacology / Q000627:therapeutic use; D044466:Asian People; D005260:Female; D005424:Flecainide / Q000097:blood* / Q000494:pharmacology / Q000627:therapeutic use; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D062554:NAV1.5 Voltage-Gated Sodium Channel / Q000235:genetics*; D011401:Promoter Regions, Genetic; D013617:Tachycardia, Supraventricular / Q000188:drug therapy / Q000235:genetics
chemical_list: D000889:Anti-Arrhythmia Agents; D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human; D005424:Flecainide