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 amongABCB1c.3435C>T, c.2677G>A/T, c.1236C>T,ABCG2c.421C>A,CYP3A5*3andCYP2J2*7genotypes. 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.