LAUSR

Supplemental Digital Content is Available in the Text. Introduction: The authors aimed to examine the impact of single nucleotide polymorphisms in P-glycoprotein, the hepatic uptake transporter organic anion transporter protein 1B1, cytochrome P450 (CYP) 3A5, and carboxylesterase-1 (CES1) on the steady-state dose-adjusted trough concentrations of edoxaban (CEdo/D) and M-4 (CM-4/D). They also investigated whether CM-4 and CEdo affect prothrombin time (PT). Methods: The analyses included 152 patients with nonvalvular atrial fibrillation (NVAF) undergoing AF catheter ablation. The CYP3A5*3; CES1 c.1168-33A>C, c.257+885T>C; SLCO1B1 c.388A>G, c.521T>C; and ABCB1 c.3435C>T, c.2677G>A/T, c.1236C>T genotypes were determined. Results: Stepwise selection multiple linear regression analyses demonstrated that creatinine clearance (Ccr), concomitant use of amiodarone, and SLCO1B1*15 haplotype status were independent factors influencing CM-4/D (partial R2 = 0.189, 0.098, 0.067, respectively, all P values < 0.005). Ccr and concomitant use of amiodarone were independent factors influencing CEdo/D (partial R2 = 0.260, 0.117, respectively, both P value < 0.001). CEdo and CM-4 showed a weak correlation with PT (ρ = 0.369 and 0.315, both P values < 0.001). Conclusions: Although information concerning Ccr, concomitant use of amiodarone, and SLCO1B1*15 haplotype may be useful in assessing the pharmacokinetics of edoxaban, further studies are needed to clarify the requirement of PT monitoring at the trough level for dose adjustment of edoxaban in patients with NVAF.