• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

新型ROCK2抑制剂TDI01的模型引导药物研发：群体药代动力学研究与模拟

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

作者信息

Ji Xiwei, Cui Yimin

机构信息

Institute of Clinical Pharmacology, Peking University First Hospital, Beijing, China.

出版信息

Front Pharmacol. 2025 Mar 4;16:1477607. doi: 10.3389/fphar.2025.1477607. eCollection 2025.

DOI:10.3389/fphar.2025.1477607
PMID:40103594
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11913679/
Abstract

INTRODUCTION

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.

METHODS

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.

RESULTS

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.

DISCUSSION

The established model and simulation provide a useful approach to maximize the clinical medication safety and therapeutic efficacy of TDI01.

摘要

引言

TDI01是一种新型的高选择性ROCK2抑制剂，为治疗新型冠状病毒肺炎所致的急性肺损伤/急性呼吸窘迫综合征提供了一个潜在的有价值的候选药物。

方法

本研究的目的是建立群体药代动力学（Pop-PK）模型来表征TDI的药代动力学特性，并通过基于模型的模拟来指导合适临床给药方案的选择。

结果

已完成的临床研究显示出双峰现象，这在单次给予TDI01后即可观察到。因此，开发了一个具有剂量效应和肝肠循环的单室模型来描述TDI01在体内的药代动力学特征。模拟结果表明，在测试的给药方案下，多次给药后观察到的药物蓄积不会影响TID01使用的安全性。

讨论

所建立的模型和模拟为最大化TDI01的临床用药安全性和治疗效果提供了一种有用的方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2aac/11913679/168cb29c6359/fphar-16-1477607-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2aac/11913679/2912c6bc7420/fphar-16-1477607-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2aac/11913679/ccfe4109b70f/fphar-16-1477607-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2aac/11913679/0004b8a1d41d/fphar-16-1477607-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2aac/11913679/9fda98fae551/fphar-16-1477607-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2aac/11913679/5020a485903c/fphar-16-1477607-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2aac/11913679/168cb29c6359/fphar-16-1477607-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2aac/11913679/2912c6bc7420/fphar-16-1477607-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2aac/11913679/ccfe4109b70f/fphar-16-1477607-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2aac/11913679/0004b8a1d41d/fphar-16-1477607-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2aac/11913679/9fda98fae551/fphar-16-1477607-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2aac/11913679/5020a485903c/fphar-16-1477607-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2aac/11913679/168cb29c6359/fphar-16-1477607-g006.jpg

相似文献

1
Model-informed drug development of novel ROCK2 inhibitor TDI01: population pharmacokinetic study and simulation.新型ROCK2抑制剂TDI01的模型引导药物研发：群体药代动力学研究与模拟
Front Pharmacol. 2025 Mar 4;16:1477607. doi: 10.3389/fphar.2025.1477607. eCollection 2025.
2
Deficiency of endothelial FGFR1 signaling via upregulation of ROCK2 activity aggravated ALI/ARDS.内皮细胞 FGFR1 信号通路的缺失通过 ROCK2 活性的上调加重了 ALI/ARDS。
Front Immunol. 2023 Mar 10;14:1041533. doi: 10.3389/fimmu.2023.1041533. eCollection 2023.
3
Model-Informed Drug Development, Pharmacokinetic/Pharmacodynamic Cutoff Value Determination, and Antibacterial Efficacy of Benapenem against .贝那配南通过模型指导药物研发、药代动力学/药效学截断值确定及其对 的抗菌疗效
Antimicrob Agents Chemother. 2020 Feb 21;64(3). doi: 10.1128/AAC.01751-19.
4
A population pharmacokinetic study to accelerate early phase clinical development for a novel drug, teriflunomide sodium, to treat systemic lupus erythematosus.一项群体药代动力学研究，旨在加速新型药物特立氟胺钠治疗系统性红斑狼疮的早期临床开发。
Eur J Pharm Sci. 2019 Aug 1;136:104942. doi: 10.1016/j.ejps.2019.05.020. Epub 2019 May 30.
5
Population-pharmacokinetic/pharmacodynamic model of atractylodes lancea (Thunb.) DC. administration in patients with advanced-stage intrahepatic cholangiocarcinoma: a dosage prediction.苍术（Thunb.）DC. 在晚期肝内胆管癌患者中的群体药代动力学/药效学模型：剂量预测。
BMC Complement Med Ther. 2024 Nov 6;24(1):384. doi: 10.1186/s12906-024-04618-8.
6
Evaluation of the performance of a prior tacrolimus population pharmacokinetic kidney transplant model among adult allogeneic hematopoietic stem cell transplant patients.评估他克莫司群体药代动力学肾移植模型在成人异基因造血干细胞移植患者中的性能。
Clin Transl Sci. 2021 May;14(3):908-918. doi: 10.1111/cts.12956. Epub 2021 Jan 27.
7
Population Target-Mediated Pharmacokinetic/Pharmacodynamic Modeling to Evaluate SPI-62 Exposure and Hepatic 11β-Hydroxysteroid Dehydrogenase Type 1 (HSD-1) Inhibition in Healthy Adults.人群靶标介导的药代动力学/药效动力学模型评价健康成年人中 SPI-62 的暴露和肝 11β-羟甾类脱氢酶 1（HSD-1）抑制作用。
Clin Pharmacokinet. 2023 Sep;62(9):1275-1288. doi: 10.1007/s40262-023-01278-8. Epub 2023 Jul 15.
8
Nedosiran population pharmacokinetic and pharmacodynamic modelling and simulation to guide clinical development and dose selection in patients with primary hyperoxaluria type 1.内多西兰人群药代动力学和药效学建模与模拟指导 1 型原发性高草酸尿症患者的临床开发和剂量选择。
Br J Clin Pharmacol. 2024 Dec;90(12):3176-3189. doi: 10.1111/bcp.16194. Epub 2024 Aug 7.
9
Population Pharmacokinetic and Pharmacodynamic Modeling and Effects on Platelet Counts of Different Dosages of Eltrombopag in Chinese Patients With Chronic Primary Immune Thrombocytopenia.中国慢性原发性免疫性血小板减少症患者中不同剂量艾曲泊帕的群体药代动力学和药效学建模及其对血小板计数的影响
Clin Ther. 2015 Jul 1;37(7):1382-95. doi: 10.1016/j.clinthera.2015.03.024. Epub 2015 Apr 27.
10
Model-Informed Drug Development of New Cefoperazone Sodium and Sulbactam Sodium Combination (3:1): Pharmacokinetic/Pharmacodynamic Analysis and Antibacterial Efficacy Against Enterobacteriaceae.新型头孢哌酮钠舒巴坦钠（3:1）的模型引导药物研发：药代动力学/药效学分析及对肠杆菌科细菌的抗菌疗效
Front Pharmacol. 2022 Jul 18;13:856792. doi: 10.3389/fphar.2022.856792. eCollection 2022.

本文引用的文献

1
Deficiency of endothelial FGFR1 signaling via upregulation of ROCK2 activity aggravated ALI/ARDS.内皮细胞 FGFR1 信号通路的缺失通过 ROCK2 活性的上调加重了 ALI/ARDS。
Front Immunol. 2023 Mar 10;14:1041533. doi: 10.3389/fimmu.2023.1041533. eCollection 2023.
2
Characteristics of SARS-CoV-2 and COVID-19.SARS-CoV-2 和 COVID-19 的特征。
Nat Rev Microbiol. 2021 Mar;19(3):141-154. doi: 10.1038/s41579-020-00459-7. Epub 2020 Oct 6.
3
Thoughtflow: Standards and Tools for Provenance Capture and Workflow Definition to Support Model-Informed Drug Discovery and Development.
思维流程：用于来源捕获和工作流定义以支持模型驱动药物发现与开发的标准和工具。
CPT Pharmacometrics Syst Pharmacol. 2017 May;6(5):285-292. doi: 10.1002/psp4.12171. Epub 2017 May 15.
4
Good Practices in Model-Informed Drug Discovery and Development: Practice, Application, and Documentation.模型引导的药物发现与开发中的良好实践：实践、应用与文档记录
CPT Pharmacometrics Syst Pharmacol. 2016 Mar;5(3):93-122. doi: 10.1002/psp4.12049. Epub 2016 Mar 14.
5
Optimizing oncology therapeutics through quantitative translational and clinical pharmacology: challenges and opportunities.通过定量转化和临床药理学优化肿瘤治疗：挑战与机遇
Clin Pharmacol Ther. 2015 Jan;97(1):37-54. doi: 10.1002/cpt.7. Epub 2014 Dec 9.
6
Modeling and Simulation Workbench for NONMEM: Tutorial on Pirana, PsN, and Xpose.NONMEM 模型与仿真工作平台：Pirana、PsN 和 Xpose 使用教程。
CPT Pharmacometrics Syst Pharmacol. 2013 Jun 26;2(6):e50. doi: 10.1038/psp.2013.24.
7
Likelihood based approaches to handling data below the quantification limit using NONMEM VI.使用NONMEM VI基于似然法处理低于定量限的数据。
J Pharmacokinet Pharmacodyn. 2008 Aug;35(4):401-21. doi: 10.1007/s10928-008-9094-4. Epub 2008 Aug 7.
8
PsN-Toolkit--a collection of computer intensive statistical methods for non-linear mixed effect modeling using NONMEM.PsN工具包——一组使用NONMEM进行非线性混合效应建模的计算机密集型统计方法。
Comput Methods Programs Biomed. 2005 Sep;79(3):241-57. doi: 10.1016/j.cmpb.2005.04.005.
9
Perl-speaks-NONMEM (PsN)--a Perl module for NONMEM related programming.Perl 语言的 NONMEM 工具（PsN）——一个用于 NONMEM 相关编程的 Perl 模块。
Comput Methods Programs Biomed. 2004 Aug;75(2):85-94. doi: 10.1016/j.cmpb.2003.11.003.
10
Ways to fit a PK model with some data below the quantification limit.用一些低于定量限的数据拟合药代动力学（PK）模型的方法。
J Pharmacokinet Pharmacodyn. 2001 Oct;28(5):481-504. doi: 10.1023/a:1012299115260.