Chan, Stella Sze WaStella Sze WaChanHu, M.Yang, Y.-L.Fok, B. S. P.Chu, T. T. W.Poon, E. W. M.Yin, O. Q. P.Lee, V. H. L.Tomlinson, B.2023-06-192023-06-192012https://repository.sfu.edu.hk/handle/sfu/4042<b>Background:</b> 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. <b>Methods:</b> 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. <b>Results:</b> 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 (AUC_o–∞) 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. <b>Conclusions:</b> 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.enjournal article10.1515/dmdi-2011-0032