The final, formatted version of the article will be published soon.
ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Pharmacogenetics and Pharmacogenomics
Volume 15 - 2024 |
doi: 10.3389/fphar.2024.1454612
This article is part of the Research Topic Advances in Pharmacogenomics: Basic, Translational, and Clinical View all 10 articles
Population pharmacokinetic study of the effect of polymorphisms in the ABCB1 and CES1 genes on the pharmacokinetics of dabigatran
Provisionally accepted
Zhuan Yang
1,2*
Wen R. Tan
3
Qin Li
1*
Ying Wang
1*
Shijing Liu
1*
Lu Chen
1
Yan Zhou
1*
Chen Zeng
1*
Yan Zeng
1*
Yun Xiong
1*
Qian Zhang
1*
Na Li
1*
Peng Du
1*
Lin Liu
1*
Jiyu Chen
1,2*
Yan He
1,2*- 1 Clinicla Trials Center, the Affiliated Hospital of Guizhou Medical University, Guiynang, China
- 2 School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang, Guizhou Province, China
- 3 Department of Pharmacology and Systems Physiology, College of Medicine, University of Cincinnati, Cincinnati, Ohio, United States
The impact of genetic polymorphisms in the ABCB1 and CES1 genes on dabigatran plasma concentrations remains a subject of debate, and the purpose of this study was to quantitatively assess the effects of genetic polymorphisms on dabigatran esters in healthy Chinese subjects employed a population pharmacokinetic (PopPK) approach.Methods: In total, 1,926 pharmacokinetic (PK) samples from 123 healthy individuals who were given 150 mg of dabigatran orally during a fasting state or postprandially were analyzed using the PopPK model. A two-compartment model with first-order absorption was found to adequately describe the PK data.The results showed that covariates food intake and ABCB1 SNP rs4148738 were shown to have statistically significant impacts. Specifically, in postprandial administration increased lag time (ALAG) and clearance (CL) by 2.65% and 0.51%, respectively, and decreased absorption rate constant (KA) by 0.24%. Additionally, in subjects with CT genotype ABCB1 (rs4148738), the central ventricular volume of distribution (V2) was increased by 0.38%.In summary, the PopPK model developed in this study was robust and effectively characterized the pharmacokinetics of dabigatran in healthy Chinese adults, demonstrating that both food and ABCB1 genetic variation significantly influence the absorption and plasma concentration levels of dabigatran.
Keywords: population pharmacokinetic1, food effects2, dabigatran3, genetic polymorphism4, ABCB15, CES16
Received: 25 Jun 2024; Accepted: 29 Oct 2024.
Copyright: © 2024 Yang, Tan, Li, Wang, Liu, Chen, Zhou, Zeng, Zeng, Xiong, Zhang, Li, Du, Liu, Chen and He. 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:
Zhuan Yang, Clinicla Trials Center, the Affiliated Hospital of Guizhou Medical University, Guiynang, China
Qin Li, Clinicla Trials Center, the Affiliated Hospital of Guizhou Medical University, Guiynang, China
Ying Wang, Clinicla Trials Center, the Affiliated Hospital of Guizhou Medical University, Guiynang, China
Shijing Liu, Clinicla Trials Center, the Affiliated Hospital of Guizhou Medical University, Guiynang, China
Yan Zhou, Clinicla Trials Center, the Affiliated Hospital of Guizhou Medical University, Guiynang, China
Chen Zeng, Clinicla Trials Center, the Affiliated Hospital of Guizhou Medical University, Guiynang, China
Yan Zeng, Clinicla Trials Center, the Affiliated Hospital of Guizhou Medical University, Guiynang, China
Yun Xiong, Clinicla Trials Center, the Affiliated Hospital of Guizhou Medical University, Guiynang, China
Qian Zhang, Clinicla Trials Center, the Affiliated Hospital of Guizhou Medical University, Guiynang, China
Na Li, Clinicla Trials Center, the Affiliated Hospital of Guizhou Medical University, Guiynang, China
Peng Du, Clinicla Trials Center, the Affiliated Hospital of Guizhou Medical University, Guiynang, China
Lin Liu, Clinicla Trials Center, the Affiliated Hospital of Guizhou Medical University, Guiynang, China
Jiyu Chen, Clinicla Trials Center, the Affiliated Hospital of Guizhou Medical University, Guiynang, China
Yan He, Clinicla Trials Center, the Affiliated Hospital of Guizhou Medical University, Guiynang, 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.