S-Space College of Medicine/School of Medicine (의과대학/대학원) Pharmacology (약리학전공) Journal Papers (저널논문_약리학전공)
Pharmacokinetic interaction of flecainide and paroxetine in relation to the CYP2D6*10 allele in healthy Korean subjects
- Lim, Kyoung Soo; Cho, Joo-Youn; Jang, In-Jin; Kim, Bo-Hyung; Kim, JaeWoo; Jeon, Ji-Young; Tae, Yu-Mi; Yi, SoJeong; Eum, SoYoung; Shin, Sang-Goo; Yu, Kyung-Sang
- Issue Date
- Br J Clin Pharmacol. 2008; 66(5): 660-6
- Anti-Anxiety Agents/blood/*pharmacokinetics; Anti-Arrhythmia Agents/blood/*pharmacokinetics; Area Under Curve; Cross-Over Studies; Cytochrome P-450 CYP2D6/antagonists & inhibitors/*genetics; Drug Administration Schedule; Drug Interactions/genetics; Flecainide/blood/*pharmacokinetics; Genotype; Half-Life; Humans; Korea; Male; Metabolic Clearance Rate; Paroxetine/blood/*pharmacokinetics; *Polymorphism, Genetic; Statistics, Nonparametric; Statistics, Nonparametric
- AIMS: 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.
- 1365-2125 (Electronic)
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