Impact of gene polymorphisms in drug‐metabolizing enzymes and transporters on trough concentrations of rivaroxaban in patients with atrial fibrillation

Rivaroxaban is excreted from the body via multiple pathways involving glomerular filtration, drug‐metabolizing enzymes and transporters. In this study, we aimed to examine the impact of single nucleotide polymorphisms in P‐glycoprotein, breast cancer resistance protein, cytochrome P450 (CYP) 3A5 and CYP2J2 on the pharmacokinetics of rivaroxaban. Eighty‐six patients with non‐valvular atrial fibrillation (NVAF) undergoing AF catheter ablation were enrolled in this study. In these analyses, the dose‐adjusted plasma trough concentration ratio (C 0h /D) of rivaroxaban was used as the pharmacokinetic index. The median (quartile range) rivaroxaban C 0h /D was 3.39 (2.08‐5.21) ng/mL/mg (coefficient of variation: 80.5%). The C 0h /D did not differ significantly among ABCB1 c.3435C>T, c.2677G>A/T, c.1236C>T, ABCG2 c.421C>A, CYP3A5*3 and CYP2J2*7 genotypes. Stepwise selection multiple linear regression analysis showed that the estimated glomerular filtration rate was the only independent factor influencing the C 0h /D of rivaroxaban ( R 2 = 0.152, P < 0.001). There was a significant correlation between the C 0h of rivaroxaban and prothrombin time (PT) ( rho = 0.357, P = 0.001). In patients with NVAF, pharmacokinetic genotype tests are unlikely to be useful for prediction of the C 0h of rivaroxaban.