人工肠模拟器. 一个用于预测弱基本BCS-II药物,二皮里达摩尔的肠道和血度-时间概况的方案
Krutika Meena Harish Jain1, Ishaan Duggal1, Hao Helen Hou2
1Department of Pharmaceutics, University of Minnesota, Minneapolis, MN 55455, USA.
概括
这项研究开发了一个人工肠道模拟器 (AGS) 来预测体内的药物度. AGS精确模拟了二甲基 (DPD) 的吸收,显示了其在预测弱基药物的生物可用性方面的潜力.
科学领域:
- 药理动力学 药理动力学
- 药物输送系统 药物输送系统
- 计算建模 计算建模
背景情况:
- 预测体内的药物行为对于药物开发至关重要.
- 弱基药物 (BCS-II) 由于溶解性和吸收变异性而带来挑战.
- 现有的 in vitro 方法可能不能准确地反映 in vivo 条件.
研究的目的:
- 开发一个用于肠道和血二皮里达摩尔 (DPD) 度-时间概况的预测模型.
- 将人工肠道模拟器 (AGS) 与处置模型集成,以提高预测准确度.
- 模拟BCS-II药物的生理相关的吸收率.
主要方法:
- 使用DPD的静脉注射血度数据,开发了一个3个隔间处置模型.
- 使用了一个具有捐赠细胞和空洞纤维吸收模块的AGS.
- 模拟胃空气通过增量DPD剂量添加到AGS捐赠者.
主要成果:
- 预测的DPD血度-时间概况与50毫克口服剂量的人体体体内数据相匹配.
- 对30毫克和90毫克剂量的模拟十二指管度和沉分数与人类测量结果一致.
- AGS在一个生理上相关的速率常数 (0.0402分−1) 上成功吸收了 DPD.
结论:
- 模拟体外生理吸收率对于准确预测BCS-II化合物的生物利用率至关重要.
- 集成的AGS和处置模型为体外-体外抽取提供了一个强大的平台.
- 这种方法为BCS-II药物进行传统溶解测试提供了更相关的替代方案.
相关概念视频
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