通过细胞层进行溶解物运输的特征:从简化的三隔间模型中对人工物进行校正和参数提取
Júlia Tárnoki-Zách1, Imre Boldizsár2, Gábor M Kovács3
1Department of Biological Physics, Eotvos University, Budapest, Hungary.
概括
自动表皮屏障测试可以具有采样文物. 我们开发了一个数学校正和一个三模型,以便更准确地进行药物吸收和生物可用性分析.
科学领域:
- 药理学和药物开发领域
- 生物物理化学 生物物理化学
- 计算生物学 计算生物学
背景情况:
- 穿孔插件上的上皮细胞层对于早期药物开发至关重要,估计吸收和生物可用性.
- 在这些试验中,自动取样增加了吞吐量,但可以引入诸如残余体积和表面吸附等工件.
- 这些人工物扭曲了度时间序列,影响了下游的药理动力学分析.
研究的目的:
- 为了开发一个数学纠正采样器件在transwell测试中的文物.
- 实施一个三分区模型来分析通过上皮屏障的溶液运输.
- 为了使分析物相互作用和化合物行为在体外更准确地进行表征.
主要方法:
- 提出了一个数学校正方法来考虑采样文物.
- 开发了一种三隔间模型,以捕捉膜扩散,细胞封存和代谢损失.
- 通过穿上皮质屏障运输试验的数据集来演示该方法.
主要成果:
- 数学纠正有效地解决了度时间序列中的系统文物.
- 三个隔间模型提供了与明显透性 (Papp) 相比,在机械上有意义的参数.
- 这种方法提高了分析物与上皮细胞层相互作用的特征的准确性.
结论:
- 拟议的方法可以提高跨井测试中自动测量的精度.
- 三分区模型提供了比传统方法更强大的溶液运输分析.
- 这种方法支持在体外输送系统中更好地评估药物行为.
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