Effects of CYP2D6*10, CYP3A5*3, CYP1A2*1F, and ABCB1 C3435T polymorphisms on the pharmacokinetics of flecainide in healthy Chinese subjects
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Miao Hu
Abstract
Background: Although flecainide is thought to be metabolized predominantly by cytochrome P450 (CYP) 2D6, it shows pharmacokinetic interactions with drugs, such as verapamil and digoxin, which may suggest other CYP pathways or ATP-binding cassette (ABC) transporters might be involved. This study evaluated effects of common polymorphisms in Chinese in CYP2D6, CYP3A5, CYP1A2, and ABCB1 on flecainide pharmacokinetics.
Methods: Single oral 100-mg doses of flecainide were given to 15 healthy male Chinese subjects who were genotyped for the CYP2D6*2, *5, *10, CYP3A5*3, CYP1A2*1F and ABCB1 C1236T, G2677T/A, and C3435T polymorphisms.
Results: There was no significant difference in the pharmacokinetics of flecainide among CYP2D6 (mainly involving *10) genotypes. The CYP3A5*3/*3 subjects (n=8) had a 26% higher systemic exposure (AUC0–∞) and 17% lower apparent oral clearance of flecainide than the combined group of CYP3A5*1/*1 (n=6) and CYP3A5*1/*3 (n=1) subjects (p<0.05). Subjects homozygous for CYP1A2*1F tended to have lower systemic exposure and increased clearance of flecainide compared to those with CYP1A2*1A/1F in subjects with at least one CYP2D6 variant allele.
Conclusions: The disposition of flecainide appeared to be influenced by the CYP3A5*3 and possibly the CYP1A2*1F polymorphisms, particularly in subjects with CYP2D6 variant alleles.
©2012 by Walter de Gruyter Berlin Boston
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- Editorial
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- Effects of CYP2D6*10, CYP3A5*3, CYP1A2*1F, and ABCB1 C3435T polymorphisms on the pharmacokinetics of flecainide in healthy Chinese subjects
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- Masthead
- Masthead
Articles in the same Issue
- Editorial
- Cytochrome P450 enzymes
- Reviews
- The aryl hydrocarbon receptor system
- Herb-drug interactions with Danshen (Salvia miltiorrhiza): a review on the role of cytochrome P450 enzymes
- Pharmacokinetic interactions of selective serotonin reuptake inhibitors with other commonly prescribed drugs in the era of pharmacogenomics
- Original Articles
- Effects of CYP2D6*10, CYP3A5*3, CYP1A2*1F, and ABCB1 C3435T polymorphisms on the pharmacokinetics of flecainide in healthy Chinese subjects
- Analysis of the molecular interactions and complexation of chloroquine with bovine serum albumin
- The microstructure of DNA-egg yolk phosphatidylcholine-gemini surfactants complexes: effect of the spacer length
- Meeting Reports
- Report from the European Society of Pharmacogenomics and Theranostics (ESPT) Inaugural Symposium 2011 in Bled
- Pharmacogenetics in Latin American populations: regulatory aspects, application to herbal medicine, cardiovascular and psychiatric disorders
- Masthead
- Masthead
