使用小气道微生理系统评估药物透性的评估
Robert M Geiger1, Shekh M Rahman1, Md Shadiqur Rashid Roni1
1Division of Applied Regulatory Science, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, United States Food and Drug Administration, Silver Spring, MD, United States.
Frontiers in pharmacology
|August 1, 2025
概括
一个新的微生理系统 (MPS) 准确地预测了吸入药物的透性,将阿尔布特罗尔硫酸盐和福莫特罗尔烟酸盐分类为高度透性和奥洛达特罗尔酸盐分类为低透性. 该系统通过提供可靠的透性数据来增强药物开发.
科学领域:
- 药理学 药理学是指药理学的学科.
- 生物技术是生物技术.
- 药物运输 药物运输 药物运输
背景情况:
- 准确预测吸入药物的透性对于新药和仿制药的开发至关重要.
- 传统的二维细胞培养缺乏肺微环境的生理相关性.
- 一个小型呼吸道微生理系统 (MPS) 提供了一个更准确的体外模型.
研究的目的:
- 为了评估一个小的气道MPS测量吸入药物的透性.
- 评估系统能够重复肺空气液体接口 (ALI) 的能力.
主要方法:
- 在ALI培养的初级人类肺上皮细胞,其次是内皮细胞共同培养.
- 量化了药物与聚二甲基 (PDMS) 材料的非特异性结合.
- 药物透性是通过量化化合物随着时间的推移而测量的.
主要成果:
- 该MPS成功复制了肺细胞类型和形态.
- 甲醇硫酸盐,甲醇 fumarate 和 olodaterol HCl 显示无意义的非特异性结合.
- 黄酸表现出显著的非特异性结合,并被排除在外.
- 对于每个化合物,确定了表面透率 (Papp) 值.
结论:
- 小气道MPS为吸入药物透性提供了一个生理上相关的模型.
- 硫酸醇和硫酸醇是高度透的;醇酸是低透的.
- 这种MPS可以改善 in vivo 预测吸入药物的行为.
相关概念视频
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354