Effect of ABCB1 SNP polymorphisms on the plasma concentrations and clinical outcomes of rivaroxaban in Chinese NVAF patients: a population pharmacokinetic-based study

作者：Fei Wang, Ze Li, Youqi Huang, Qin Liu, Libin Zhao, Honghong Wang, Hongjin Gao, Mingyu Chen, Mingyu Chen, Yuze Lin, Xingang Li, Min Chen, Min Chen · 发表于：Frontiers in Pharmacology · 年份：2025 · DOI：10.3389/fphar.2025.1574949 · 被引用次数：4 · 研究领域：Atrial Fibrillation Management and Outcomes、Blood Coagulation and Thrombosis Mechanisms、Antiplatelet Therapy and Cardiovascular Diseases

Background This study utilized a population pharmacokinetic (PPK) approach to assess the influence of ABCB1 genetic polymorphisms on the plasma concentrations and clinical outcomes of rivaroxaban. Methods The PPK model for rivaroxaban was developed using the nonlinear mixed-effects modelling approach and Monte Carlo simulations were employed to derive peak concentration (C max ) and trough concentration (C trough ). ABCB1 genetic variants were analyzed for their impact on the plasma concentrations and clinical outcomes. Results Analysis of 287 rivaroxaban plasma concentrations from 228 non-valvular atrial fibrillation (NVAF) patients revealed significant associations between AST (aspartate aminotransferase)/ALT (alanine aminotransferase) ratios and the apparent clearance (CL/F), the apparent volume of distribution (V/F). ABCB1 1236C>T TT and ABCB1 c.2482-2236C>T CC genotypes exhibited higher dose-adjusted C max (C max /D) compared to other relevant genotypes. Additionally, the ABCB1 3435C>T TT genotype showed lower dose-adjusted C trough (C trough /D) compared to CC or CT genotypes. For clinical outcomes, the ABCB1 c.2482–2236C>T CC genotype had a higher bleeding risk compared to TT (RR = 1.99, 95% CI 1.08–3.69) or CT genotypes (RR = 1.42, 95% CI 1.04–1.92), and ABCB1 3435C>T TT genotype showed a higher thromboembolic risk compared to CC genotype (RR = 3.48, 95% CI 1.02–11.85). Conclusion The PPK model incorporated CL/F and V/F with the cova...