将阿尔蒂斯复制体器官系统与MDCK单层进行比较,以预测莱纳利多米德的口服吸收
Cole S Hudson1, Jonathan Cheong2, Jesse Yu2
1Department of Pharmacological & Pharmaceutical Sciences, University of Houston College of Pharmacy, Houston, TX 77004, USA.
Pharmaceutics
|September 27, 2025
概括
与传统的细胞模型相比,人类肠道有机体提供了更准确的口服药物吸收预测,如lenalidomide. 这些有机体更好地解释载体效应,改善体内吸收预测.
科学领域:
- 药理学 药理学是指药理学的学科.
- 药物开发 药物开发
- 生物技术是生物技术.
背景情况:
- 预测口服药物吸收在早期药物开发中至关重要.
- 像PAMPA和MDCK细胞这样的常规体外模型对某些药物类别有局限性.
- 人类肠道有机体是预测药物吸收的新兴,有希望的替代品.
研究的目的:
- 使用人类肠道有机物衍生的单层来预测lenalidomide的口服吸收.
- 为了在有机体模型中比较lenalidomide的透性与常规细胞系.
- 通过工程细胞系来评估载体在莱纳利多米德吸收中的作用.
主要方法:
- 人类阴茎器官 (RepliGut®) 被培养成单层.
- 莱纳利多米德的透性在有机单层和各种MDCK细胞系 (野生型,P-gp淘汰,P-gp过度表达,BCRP过度表达) 中进行了评估.
- 在小鼠体内进行了lenalidomide的口服和静脉注射,随后进行了药理动力学分析.
主要成果:
- 列纳利多米德在老鼠中显示出高的口服生物可用性 (68-120%).
- 人类肠道有机体显示,莱纳利多米德的表面透率 (Papp) 约为0.6 × 10−6 cm/s,不论度如何.
- 列纳利多米德帕普在gMDCK细胞中较低 (~0.2 × 10−6 cm/s),并在相关细胞模型中被确定为P-gp/BCRP基质.
结论:
- 马丁 - 达比犬 (MDCK) 细胞透率低估了莱纳利多米德体内吸收.
- 器官系统在捕捉载体介导和细胞对药物透性的影响方面显得优越.
- 与传统的基于细胞的测定相比,肠道器官可以提供更准确的口服药物吸收预测.
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