title: Pharmacokinetic interaction of flecainide and paroxetine in relation to the CYP2D6*10 allele in healthy Korean subjects.
abstract: OBJECTIVE
  The objectives were to evaluate the effect of CYP2D6 genetic polymorphism on the pharmacokinetics of flecainide, and also on the extent of drug interaction with paroxetine as a CYP2D6 inhibitor after a single oral administration in healthy subjects.
  
  
  METHODS
  An open-label, two-period, single-sequence, cross-over study was performed in 21 healthy Korean male volunteers (seven for CYP2D6*1/*1 or *1/*2, group 1; seven for CYP2D6*1/*10, group 2; seven for CYP2D6*10/*10 or *10/*36, group 3). Subjects were administered 200 mg of flecainide on day 1. After a 7-day wash-out period, subjects were administered 20 mg of paroxetine from day 8 to 14, and 200 mg of flecainide on day 15. Blood sampling was performed up to 72 h after flecainide administration.
  
  
  RESULTS
  Terminal elimination half-life and mean residence time (MRT) were significantly different among three genotype groups after a single oral administration of flecainide (P = 0.021, 0.011, respectively). Area under the concentration-time curve, terminal elimination half-life and MRT increased significantly after paroxetine co-administration only in groups 1 and 2.
  
  
  CONCLUSIONS
  This study reports that the extent of drug interaction between flecainide and paroxetine is influenced by the CYP2D6*10 allele in healthy subjects, which is frequent in Asians.
authors.affiliation: Department of Pharmacology and Clinical Pharmacology, Seoul National University College of Medicine and Hospital, Seoul, Korea.
authors.forename: Kyoung Soo
authors.initials: KS
authors.lastname: Lim
authors.forename: Joo-Youn
authors.initials: JY
authors.lastname: Cho
authors.forename: In-Jin
authors.initials: IJ
authors.lastname: Jang
authors.forename: Bo-Hyung
authors.initials: BH
authors.lastname: Kim
authors.forename: JaeWoo
authors.initials: J
authors.lastname: Kim
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Jeon
authors.forename: Yu-Mi
authors.initials: YM
authors.lastname: Tae
authors.forename: SoJeong
authors.initials: S
authors.lastname: Yi
authors.forename: SoYoung
authors.initials: S
authors.lastname: Eum
authors.forename: Sang-Goo
authors.initials: SG
authors.lastname: Shin
authors.forename: Kyung-Sang
authors.initials: KS
authors.lastname: Yu