胆汁是粘膜机械和运输的选择性电梯
Simon Hanio1, Stephanie Möllmert2, Conrad Möckel2
1Institute for Pharmacy and Food Chemistry, University of Wuerzburg, Am Hubland, 97074 Wuerzburg, Germany.
Molecular pharmaceutics
|October 31, 2023
概括
胆汁改变肠道粘液机制和药物扩散. 与胆汁相互作用的药物显示出更快的粘液传输,影响药物吸收,如大鼠研究证实的那样.
科学领域:
- 胃肠病学 胃肠病学
- 生物物理学的生物物理.
- 药理学 药理学是指药理学的学科.
背景情况:
- 肠道粘液提供机械保护,并影响药物吸收.
- 胆汁在粘液生物力学和药物运输中的特定作用在很大程度上仍未被描述.
研究的目的:
- 为了研究胆汁对肠道粘膜生物力学的影响.
- 确定胆汁如何影响粘液层内的药物运输.
- 为了将药物胆汁相互作用与药物素相互作用以及体内生物可用性相关联.
主要方法:
- 使用Brillouin成像来评估粘液硬化动态.
- 采用差异动态显微镜来分析粘液中的药物扩散动力学.
- 在小鼠体内进行的用胆酸分离剂进行的试验.
- 根据胆汁和粘素相互作用概况对50多种药物进行了分组.
主要成果:
- 胆汁表现出平方根时间扩散动力学,并引起了暂时的粘液硬化.
- 粘液扩散在胆汁的存在下从亚扩散转变为布朗式.
- 与胆汁相互作用的药物 (Fluphenazine,Perphenazine) 在胆汁的粘液中扩散得更快.
- 非胆汁相互作用药物 (美托普罗罗尔) 的扩散保持一致.
- 鼠类研究显示,用胆酸分离剂降低了Perphenazine的生物可用性,但不是Metoprolol.
- 药物胆汁相互作用与药物素相互作用相关,但不是相反.
结论:
- 胆汁显著影响肠道粘液的生物力学和药物扩散特性.
- 药物与胆汁相互作用的能力是药物与粘液相互作用的预测因素.
- 了解胆汁-粘液-药物相互作用对于预测和优化口服药物吸收至关重要.
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