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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- First Hospital, Peking University, Beijing, China
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
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