人类和老鼠近端管在体外模型用于ADME应用
Olivia C Klatt1,2, Lenya de Brouwer1,2, Femke Hendriks1,2
1Department of Chemistry and Pharmaceutical Science, Amsterdam Institute of Molecular and Life Sciences, Vrije Universiteit Amsterdam, De Boelelaan 1108, 1081 HZ, Amsterdam, The Netherlands.
Archives of toxicology
|March 3, 2025
概括
本综述评估了脏靠近管道的体外模型,以准确预测药物清除. 目前的模型有局限性,但干细胞和有机体技术的进步显示出更好的药理动力学概况的前景.
科学领域:
- 药理学和毒理学 药理学和毒理学
- 脏生理学 脏生理学
- 生物技术是生物技术.
背景情况:
- 脏的近端管是药物和代谢物分泌的关键,显著影响药物动力学特征.
- 了解近道管中的异生体运输对于药物开发和安全性评估至关重要.
- 现有的体外模型往往无法完全复制体外近端管道的复杂运输功能.
研究的目的:
- 审查和批判性地评价现有的人体和大鼠脏近壁管道体外模型.
- 在这些模型中评估关键载体和代谢酶的表达和功能.
- 确定局限性,并提出改善清量的体外建模的解决方案.
主要方法:
- 对各种体外模型的综合文献综述:亚细胞分数,细胞系,初级培养,iPSC衍生模型,有机体和微流体系统.
- 专注于评估运输体和I/II期代谢酶的表达和功能活性.
- 人类和老鼠模型的比较分析.
主要成果:
- 现有各种各样的体外模型,每个都有特定的优点和弱点,涉及运输体和酶的表现.
- 诱导多能干细胞 (iPSC) 衍生模型和器官类型系统显示了改善生理相关性的潜力.
- 在不同模型类型的异生菌运输和新陈代谢的忠实性中存在显著的变化.
结论:
- 没有一个单一的体外模型可以完美地复制体内近位管道.
- 在iPSC技术,有机体和微流体学方面的进步为开发更具预测性的清除模型提供了有希望的途径.
- 需要进一步的研究来优化这些先进的模型,以便准确的药理动力学和毒理动力学评估.
相关概念视频
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