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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Drug Metabolism and Transport
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1477607

Model-informed drug development of novel ROCK2 inhibitor TDI01: population pharmacokinetic study and simulation

Provisionally accepted
Xiwei Ji Xiwei Ji *Yimin Cui Yimin Cui *
  • First Hospital, Peking University, Beijing, China

The final, formatted version of the article will be published soon.

    TDI01 is a novel and highly selective ROCK2 inhibitor, which provides a potential valuable candidate for the treatment of ALI/ARDS due to COVID-19. The objective of this study was to develop Pop-PK models to characterize the PK properties of TDI, and to guide the choice of suitable clinical dosage regimens via model-based simulation. The completed clinical study suggested a double peak phenomenon, which could be observed after single administration of TDI01. Thus, a one-compartment model with dosage effect and hepato-enteral circulation were developed to describe the PK profiles of TDI01 in vivo. Results from the simulation show that the drug accumulation observed after multiple doses would not affect the safety of TID01 usage under the tested dosage regimen. The established model and simulation provide a useful approach to maximize the clinical medication safety and therapeutic efficacy of TDI01.

    Keywords: Pop-PK, TDI01, hepato-enteral circulation, Model-informed drug development, simulation

    Received: 14 Nov 2024; Accepted: 10 Feb 2025.

    Copyright: © 2025 Ji and Cui. 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:
    Xiwei Ji, First Hospital, Peking University, Beijing, China
    Yimin Cui, First Hospital, Peking University, Beijing, 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.