经典肝脏清除模型的完整扩展,使用小数分布参数f
Yoo-Seong Jeong1, William J Jusko1
1Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, State University of New York at Buffalo, Buffalo, NY, 14214, USA.
Journal of pharmaceutical sciences
|June 6, 2023
概括
经典的器官清除模型是有限的. 新的统一模型,包括Rattle,Sieve,Tube和Jar模型,为药物消除提供了更加机械的方法,改善了从体外到体外数据的预测.
科学领域:
- 药理动力学和药物新陈代谢
- 生理学基础的药理动力学 (PBPK) 建模
背景情况:
- 经典的器官清除模型简化了肝脏清除机制.
- 这些模型往往忽略过渡时间延迟,并假设隔离的内在清除 (CLu,int).
研究的目的:
- 提出统一的,机械的器官清除模型,以考虑内部血液度动态.
- 通过结合像分数分布 (fd) 这样的生理参数来扩展经典模型.
主要方法:
- 重温和修改四个经典模型的微分方程.
- 开发扩展空隙模型:拉特尔,子,管道和子.
- 应用PBPK原则和分数分布参数.
主要成果:
- 扩展模型的可行性使用11个化合物的隔离 perfused 鼠肝数据来证明.
- 成功地应用模型来进行内在和系统清除的 in vitro-in vivo 推断.
- 拟议的模型提供了一个更具生理相关性的清除表示.
结论:
- ,,管和模型为理解器官清除提供了更加机械的框架.
- 这些扩展模型显示了改善体外-体内抽象和药物开发的前景.
- 统一的方法增强了清除模型的生理基础.
相关概念视频
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