碳酸缓冲剂对药物的人造膜透的影响
Shiori Ishida1, Samuel Lee2, Balint Sinko2
1Molecular Pharmaceutics Lab., College of Pharmaceutical Sciences, Ritsumeikan University, 1-1-1, Noji-higashi, Kusatsu, Shiga 525-8577, Japan.
ADMET & DMPK
|March 31, 2025
概括
小肠中的二碳酸盐缓冲体 (BCB) 减缓了脂友弱酸和基的被动药物透. 这种效应归因于BCB的缓慢中和率影响膜表面pH.
科学领域:
- 药理动力学 药理动力学
- 生物物理化学 生物物理化学
- 药物运输 药物运输 药物运输
背景情况:
- 小肠的pH值由碳酸缓冲区 (BCB) 调节.
- 对于BCB对药物膜透的影响仍未得到充分研究.
- 了解这种相互作用对于药物吸收预测至关重要.
研究的目的:
- 研究BCB对药物的被动膜透的影响.
- 在受控条件下将BCB与酸盐缓冲区 (PPB) 进行比较.
- 阐明影响生理缓冲系统中药物透性的机制.
主要方法:
- 使用μFlux装置进行透度测量.
- 开发了一种新的浮动盖子,以保持BCB的pH稳定性.
- 采用大豆莱西丁甲基涂层膜过器进行流量测量.
- 进行了ISO-pH流量测量,比较了BCB和PPB在pH值6.5的同等缓冲容量.
主要成果:
- 浮动盖子有效地减少了120分钟内BCB的pH波动.
- 与PPB相比,脂肪酸弱酸和基药物 (例如,,) 在BCB中表现出较低的有效透性 (Pe).
- 可结合和水友弱基药物的透性在BCB和PPB中都是相似的.
结论:
- 在BCB和PPB中,对脂友弱酸和基的被动膜透速度较慢.
- 减少BCB的透率可能是由于其缓慢的中和率,影响了膜表面的微环境pH值.
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