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ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Drug Metabolism and Transport
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1574949
This article is part of the Research TopicIntegrated PK/PD and Drug Metabolism Approaches in Drug Development and EvaluationView all 3 articles
Effect of ABCB1 SNP polymorphisms on the plasma concentrations and clinical outcomes of rivaroxaban in Chinese NVAF patients: a population pharmacokinetic-based study
Provisionally accepted
Fei Wang1*
Ze Li2Youqi Huang3Qin Liu1
Honghong Wang4Libin Zhao1Hongjin Gao5Mingyu Chen3Yuze Lin3
Xingang Li2*
Min Chen6*- 1Fujian Provincial Geriatric Hospital, Teaching Hospital of Fujian Medical University, Fuzhou, Fujian Province, China
- 2Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing,10050, China
- 3Shengli Clinical College of Fujian Medical University，Fuzhou 350001, China;School of Pharmacy, Fujian Medical University, Fuzhou 350004, China
- 4Department of Pharmacy, Liuzhou Hospital of Guangzhou Women and Children's Medical Center, Liuzhou, Guangxi Zhuang Region, China
- 5Department of Pharmacology, School of Pharmacy, Fujian Medical University, Fuzhou, Fujian Province, China
- 6Shengli Clinical College of Fujian Medical University; Department of Pharmacy, Fujian Provincial Hospital, Fuzhou, 350001, China
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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.The PPK model for rivaroxaban was developed using the nonlinear mixedeffects modelling approach and Monte Carlo simulations were employed to derive peak concentration (Cmax) and trough concentration (Ctrough). 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 Cmax (Cmax/D) compared to other relevant genotypes. Additionally, the ABCB1 3435C>T TT genotype showed lower dose-adjusted Ctrough (Ctrough/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 to 3.69) or CT genotypes (RR = 1.42, 95% CI 1.04 to 1.92), and ABCB1 3435C>T TT genotype showed a higher thromboembolic risk compared to CC genotype (RR = 3.48, 95% CI 1.02 to 11.85).The PPK model incorporated CL/F and V/F with the covariate AST/ALT. Model-based simulations revealed that ABCB1 1236C>T, ABCB1 c.2482-2236C>T, and ABCB1 3435C>T genotypes had significant impacts on the plasma concentrations of rivaroxaban. Specifically, ABCB1 c.2482-2236C>T and ABCB1 3435C>T genotypes were associated with bleeding events and thromboembolic events, respectively.
Keywords: Population pharmacokinetic, rivaroxaban, Non-valvular atrial fibrillation, ABCB1 genetic polymorphisms, TDM (therapeutic drug monitoring)
Received: 11 Feb 2025; Accepted: 08 Apr 2025.
Copyright: © 2025 Wang, Li, Huang, Liu, Wang, Zhao, Gao, Chen, Lin, Li and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Fei Wang, Fujian Provincial Geriatric Hospital, Teaching Hospital of Fujian Medical University, Fuzhou, Fujian Province, China
Xingang Li, Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing,10050, China
Min Chen, Shengli Clinical College of Fujian Medical University; Department of Pharmacy, Fujian Provincial Hospital, Fuzhou, 350001, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.