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Pharmacokinetic interaction of flecainide and paroxetine in relation to the CYP2D6*10 allele in healthy Korean subjects

Cited 30 time in Web of Science Cited 33 time in Scopus
Authors
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
2008-08-30
Publisher
Wiley-Blackwell
Citation
Br J Clin Pharmacol. 2008; 66(5): 660-6
Keywords
Anti-Anxiety Agents/blood/*pharmacokineticsAnti-Arrhythmia Agents/blood/*pharmacokineticsArea Under CurveCross-Over StudiesCytochrome P-450 CYP2D6/antagonists & inhibitors/*geneticsDrug Administration ScheduleDrug Interactions/geneticsFlecainide/blood/*pharmacokineticsGenotypeHalf-LifeHumansKoreaMaleMetabolic Clearance RateParoxetine/blood/*pharmacokinetics*Polymorphism, GeneticStatistics, NonparametricStatistics, Nonparametric
Abstract
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.
ISSN
1365-2125 (Electronic)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18754843

http://hdl.handle.net/10371/67552
DOI
https://doi.org/10.1111/j.1365-2125.2008.03267.x
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College of Medicine/School of Medicine (의과대학/대학원)Pharmacology (약리학전공)Journal Papers (저널논문_약리학전공)
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