狗 Mdr1 淘汰 MDCK 细胞可靠估计人类小肠透性 (Peff) 和吸收的部分 (fa)
Kristian Beran1,2, Seong Hee Park3, An Van den Bergh4
1Fraunhofer Institute for Translational Medicine and Pharmacology, 60596 Frankfurt am Main, Germany.
Molecular pharmaceutics
|September 7, 2025
概括
这项研究表明,狗Mdr1淘汰细胞系有效预测人类肠道药物吸收的透性. 这种方法有助于分类药物透性和估计口服生物可用性.
科学领域:
- 药物动力学和药物代谢
- 细胞生物学和体外模型
- 药物发现和开发
背景情况:
- 人体肠道透性显著影响药物活性成分 (API) 的口服吸收.
- 准确预测体内肠道透性对于药物开发和监管评估至关重要.
- 马丁-达比犬 (MDCK) 细胞系在体外模型中广泛用于药物透性研究.
研究的目的:
- 为预测人类肠道透性,评估内部犬类Mdr1淘汰 (cMdr1KO) MDCK细胞系.
- 为了确定体外明显透性 (Papp) 和人类有效肠道透性 (Peff) 之间的相关性.
- 评估该模型对估计口服吸收分数 (fa) 的有用性.
主要方法:
- 在不同的pH条件下使用cMdr1KO MDCK细胞系测量16种参考化合物的Papp.
- 测量Papp和确定的人类Peff值之间的相关性分析.
- 使用已确定的相关性对六种试验API进行Peff和fa的估计.
主要成果:
- 在实验室Papp和人类Peff之间观察到强烈的相关性 (R2> 0.8).
- 测试的API的估计Peff和fa值与文献数据和临床药物动力学研究良好一致.
- cMdr1 KO MDCK 模型在分类高透性亚博体育投注平台方面表现出特别有用.
结论:
- cMdr1 KO MDCK细胞系是预测人类肠道透性和药物吸收的有价值的工具.
- 这种体外模型支持准确的透性分类,特别是对于高度透的化合物.
- 这些发现支持该模型在药物发现,开发和监管提交方面得到更广泛的应用.
更多相关视频
09:24Functional Assessment of Intestinal Permeability and Neutrophil Transepithelial Migration in Mice using a Standardized Intestinal Loop Model
Published on: February 11, 2021
7.2K
10:22In Vitro and In Vivo Approaches to Determine Intestinal Epithelial Cell Permeability
Published on: October 19, 2018
25.8K
相关概念视频
01:16Methods for Studying Drug Absorption: In vitro
327
In vitro experiments are crucial for understanding the transport and absorption of drugs through biological materials. These studies employ varied methods such as the diffusion cell method, the everted sac technique, and the everted ring technique.
The diffusion cell method uses a two-compartment cell, including a donor compartment with the drug solution, which simulates the environment where the drug is applied, and a receptor compartment with a buffer solution, which simulates the environment...
The diffusion cell method uses a two-compartment cell, including a donor compartment with the drug solution, which simulates the environment where the drug is applied, and a receptor compartment with a buffer solution, which simulates the environment...
327
01:09Methods for Studying Drug Absorption: In situ
344
In situ experiments, such as the Doluisio method and Single-Pass Perfusion technique, provide critical insights into drug uptake by simulating in vivo conditions for drug absorption.
The Doluisio method involves perfusing a prepared segment of a rat's small intestine with a solution of radiolabeled drug and a non-absorbable marker. This helps to differentiate between absorbed and non-absorbed drug concentrations. The intestinal segment is connected at both ends using tubing and syringes,...
The Doluisio method involves perfusing a prepared segment of a rat's small intestine with a solution of radiolabeled drug and a non-absorbable marker. This helps to differentiate between absorbed and non-absorbed drug concentrations. The intestinal segment is connected at both ends using tubing and syringes,...
344