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Translation of a physiologically-based pharmacokinetic model for dabigatran etexilate to the design of a safety and efficacy study in post-partum women

Lookup NU author(s): Professor Farhad Kamali, Dr Paul Ayuk

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).

Abstract

© 2025 The Author(s). British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.Aims: To translate a PBPK model developed for the direct oral anticoagulant, dabigatran etexilate, the prodrug of dabigatran, based on data obtained from healthy men to healthy non-pregnant, pregnant and post-partum women. To evaluate safety and efficacy of dabigatran etexilate in post-partum women using simulations and design a future clinical study to support model verification. Methods: An integrated PBPK/PD model in healthy non-pregnant, pregnant and post-partum women was translated from the PBPK model in healthy men by capturing physiological changes. The model was also linked to established exposure-response relationships for coagulation indices and plasma-breast milk transfer using data from a pilot study. Finally, the model was used for simulation and the design of a prospective clinical study. Results: The model predicted comparable plasma concentration profiles between healthy men and healthy, pregnant and post-partum women, by capturing their physiological differences. The model also captured plasma concentration and activated partial thromboplastin time (a coagulation index) data from a pilot study in post-partum women available in the literature. A sample size of 20 and 50–60 were determined to be appropriate for safety and efficacy arms respectively, of a clinical trial for model verification. Conclusion: An integrated PBPK/PD model for dabigatran etexilate in post-partum women has been developed successfully. The model was used to design a future clinical trial examining safety and efficacy of dabigatran in postpartum women at risk of thromboembolism.

Publication metadata

Author(s): Ogungbenro K, Aucott L, Kamali F, Ayuk P

Publication type: Article

Publication status: Published

Journal: British Journal of Clinical Pharmacology

Year: 2025

Volume: 92

Issue: 4

Pages: 1109-1116

Print publication date: 01/04/2026

Online publication date: 21/11/2025

Acceptance date: 16/10/2025

Date deposited: 08/12/2025

ISSN (print): 0306-5251

ISSN (electronic): 1365-2125

Publisher: John Wiley and Sons Inc

URL: https://doi.org/10.1002/bcp.70344

DOI: 10.1002/bcp.70344

Data Access Statement: The data, model implementation and output generated in this study can be requested from the corresponding author, subject to reasonable access agreement.

PubMed id: 41273069

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