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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AbstractBackground: Although flecainide is thought to be meta-bolized 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 (n8) had a 26 higher systemic exposure (AUC 0∞) and 17 lower apparent oral clearance of flecainide than the combined group of CYP3A5*1/*1 (n6) and CYP3A5*1/*3 (n1) 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 2012.
All Author(s) ListHu M., Yang Y.-L., Fok B.S.P., Chan S.-W., Chu T.T.W., Poon E.W.M., Yin O.Q.P., Lee V.H.L., Tomlinson B.
Journal nameDrug Metabolism and Drug Interactions
Detailed descriptionTo ORKTS: duplicate record
Year2012
Month3
Day1
Volume Number27
Issue Number1
PublisherWalter de Gruyter GmbH
Place of PublicationGermany
Pages33 - 39
ISSN0334-2190
LanguagesEnglish-United Kingdom
KeywordsABCB1, CYP1A2, CYP2D6, CYP3A5, flecainide

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