在临床前研究中利用流量来告知配方策略决策
Laura I Mosquera-Giraldo1, Zina Patel2, Dongyue Yu2
1Pharmaceutical Candidate Optimization, Bristol Myers Squibb, 10300 Campus Point Drive Suite 100, San Diego, California 92121, United States.
Molecular pharmaceutics
|January 15, 2026
概括
流量测试对于选择最佳药物配方和解释体内暴露变化至关重要. 这项研究为使用流量测量,比较扩散设置,并将体外结果与体外数据相关联提供了一个框架.
科学领域:
- 制药科学 制药科学
- 药物运输 药物运输 药物运输
- 临床前研究 临床前研究
背景情况:
- 流体实验在临床前药物开发中至关重要,用于配方选择,确定超和系统的使用时间,并了解体内暴露变异性.
- 确定最佳配方需要强大的方法来评估药物透率和预测体内性能.
研究的目的:
- 建立一个决策框架,以确定基于体外流量测量的最佳药物配方.
- 为了比较两个不同的扩散设置的实用性和局限性:96孔的PermeaPad板和Pion μFLUX扩散系统.
- 为了将体外流量数据与动物模型中的体内暴露数据相关联.
主要方法:
- 在两个扩散系统中使用流体实验评估了五种内部模型化合物:96孔的PermeaPad板和Pion μFLUX.
- 使用质谱测量在接收机中评估药物度.
- 研究了无形溶解度和MDCK被动透性的对试验可检测性的影响.
主要成果:
- 96井的PermeaPad系统由于无法检测到的接收度,对某些化合物不够,因此需要转向更大的Pion μFLUX系统.
- 无形溶解度和MDCK被动透度是决定PermeaPad试验成功的关键因素.
- 在体外流体实验和动物物种体内暴露之间观察到强烈的相关性,突出了仅溶解数据的局限性.
结论:
- 流量测试是选配方和阐明体内观察到的配方依赖差异的重要工具.
- 与质谱相结合的Pion μFLUX系统,在PermeaPad板不够时,为流量测量提供了一种可靠的方法.
- 整合流量数据可以比单独的溶解数据更全面地了解药物性能.
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