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Open Access
CC BY 4.0 · Thromb Haemost
DOI: 10.1055/a-2802-3641
Original Article: Coagulation and Fibrinolysis

Edoxaban Population Pharmacokinetics in Chinese Patients with Nonvalvular Atrial Fibrillation: Model-Informed Dose Adjustment

Authors

  • Yuanrui Deng‡   ‡

    1   Department of Cardiology, Key Laboratory of Pulmonary Vascular Medicine, State Key Laboratory of Cardiovascular Disease, Center for Respiratory and Pulmonary Vascular Diseases, National Clinical Research Center of Cardiovascular Diseases, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

  • Shiyun Dai‡   ‡

    2   NHC Key Laboratory of Clinical Research for Cardiovascular Medications, National Clinical Research Center of Cardiovascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

  • Shengsong Zhu‡   ‡

    1   Department of Cardiology, Key Laboratory of Pulmonary Vascular Medicine, State Key Laboratory of Cardiovascular Disease, Center for Respiratory and Pulmonary Vascular Diseases, National Clinical Research Center of Cardiovascular Diseases, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

  • Juanjuan Jiang

    2   NHC Key Laboratory of Clinical Research for Cardiovascular Medications, National Clinical Research Center of Cardiovascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

  • Lin Chai

    2   NHC Key Laboratory of Clinical Research for Cardiovascular Medications, National Clinical Research Center of Cardiovascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

  • Zhiqiang Liu

    1   Department of Cardiology, Key Laboratory of Pulmonary Vascular Medicine, State Key Laboratory of Cardiovascular Disease, Center for Respiratory and Pulmonary Vascular Diseases, National Clinical Research Center of Cardiovascular Diseases, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

  • Xifeng Qian

    1   Department of Cardiology, Key Laboratory of Pulmonary Vascular Medicine, State Key Laboratory of Cardiovascular Disease, Center for Respiratory and Pulmonary Vascular Diseases, National Clinical Research Center of Cardiovascular Diseases, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

  • Lingtao Chong

    1   Department of Cardiology, Key Laboratory of Pulmonary Vascular Medicine, State Key Laboratory of Cardiovascular Disease, Center for Respiratory and Pulmonary Vascular Diseases, National Clinical Research Center of Cardiovascular Diseases, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

  • Song Hu

    1   Department of Cardiology, Key Laboratory of Pulmonary Vascular Medicine, State Key Laboratory of Cardiovascular Disease, Center for Respiratory and Pulmonary Vascular Diseases, National Clinical Research Center of Cardiovascular Diseases, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

  • Yucheng Gao

    3   Pharmaron Clinical Services Co., Ltd, Chengdu, China

  • Haoqi Chen

    3   Pharmaron Clinical Services Co., Ltd, Chengdu, China

  • Shijia Su

    3   Pharmaron Clinical Services Co., Ltd, Chengdu, China

  • Lu Hua

    1   Department of Cardiology, Key Laboratory of Pulmonary Vascular Medicine, State Key Laboratory of Cardiovascular Disease, Center for Respiratory and Pulmonary Vascular Diseases, National Clinical Research Center of Cardiovascular Diseases, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
    4   Fuwai Shenzhen Hospital, Chinese Academy of Medical Sciences, Shenzhen, China

  • Lei Tian

    2   NHC Key Laboratory of Clinical Research for Cardiovascular Medications, National Clinical Research Center of Cardiovascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

Funding Information This work was supported by Noncommunicable Chronic Diseases-National Science and Technology Major Project (no. 2024ZD0533000), Beijing Lisheng Cardiovascular Health Foundation, the National High-Level Hospital Clinical Research Funding (2025-GSP-ZD-2), and Fuwai Hospital Chinese Academy of Medical Sciences, Shenzhen (NCRCSZ-2023-015&NCRCSZ-2025-009).
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Graphical Abstract

Abstract

Background

Edoxaban is a novel oral anticoagulant that directly inhibits factor Xa. The ENGAGE population pharmacokinetic (PopPK) model was established using data from the ENGAGE AF-TIMI 48 trial, which included over 21,000 participants, predominantly (81%) White/Caucasian individuals. However, its applicability to Chinese patients necessitates further evaluation. This study assessed the suitability of the ENGAGE PopPK model for Chinese patients with nonvalvular atrial fibrillation (NVAF).

Methods

We analyzed 730 pharmacokinetic (PK) plasma samples from 104 Chinese NVAF patients using nonlinear mixed-effects modeling.

Results

A two-compartment model with first-order absorption and linear elimination optimally described the PK data of edoxaban in this cohort. Body weight (WT) and creatinine clearance were identified as significant covariates of apparent clearance (CL/F), and positively correlated with CL/F. Model-based simulations demonstrated that, in the 30 mg once-daily (q.d.) dosing group, patients with moderate renal impairment and low WT experienced higher systemic exposure than those with only one of these attributes. Additionally, patients with moderate renal impairment, whether alone or combined with low WT, displayed elevated steady-state trough concentrations (Cmin,ss) compared to those receiving the 60 mg q.d. dose.

Conclusion

Our PopPK model characterizes the PK profile of edoxaban in Chinese NVAF patients, identifies critical covariates influencing drug exposure, and proposes an evidence-based dosing regimen tailored to this population. This trial was registered at www.clinicaltrials.gov as #NCT05320627.

Keywords

edoxaban - PopPK model - nonvalvular atrial fibrillation - dosing regimen - bleeding risk

Data Availability Statement

The data that support the findings of the study are available from the corresponding author upon reasonable request (L.H: ethannan@126.com and L.T.: tianlei0807@163.com). The full-text version of this article contains a data supplement.


‡ These authors contributed equally to this article.


Supplementary Material



Publication History

Received: 11 June 2025

Accepted: 31 January 2026

Article published online:
12 February 2026

© 2026. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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