人类肠道肠:用于预测口服药物处置,毒性和疗效的非临床应用
Eimear T O'Mahony1, Christopher M Arian1, Kayenat S Aryeh1
1Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, WA, United States of America.
Pharmacology & therapeutics
|May 21, 2025
概括
人体肠状系统通过模仿人类肠道来提供先进的药物开发. 这些模型改善了口服药物处置,毒性和治疗疗效的预测.
科学领域:
- 胃肠病学和肝病学
- 药理学和毒理学 药理学和毒理学
- 再生医学是一种再生医学.
背景情况:
- 传统的体外模型不能完全复制人类肠道生理学.
- 由LGR5+干细胞衍生出来的人体肠系统,提供了一个更准确的体内类似模型.
- 体保持了捐赠者特定的遗传特征和关键的肠道功能.
研究的目的:
- 审查人类体系统在非临床药物开发中的应用.
- 为了与现有的和新兴的体外小肠模型比较肠道模型.
- 突出体在预测药物处置,毒性和疗效方面的实用性.
主要方法:
- 关于药物开发中人类体系统的当前文献的综述.
- 与其他体外肠道模型相比,体模型的性能进行比较.
- 在预测口服药物排放 (透性,新陈代谢,相互作用) 中对体应用的分析.
- 在评估药物诱导的毒性和治疗肠道疾病的疗效时评估肠体实用性的评估.
主要成果:
- 体系统准确地回顾了人类肠道的微解剖学和生理学.
- 它们在预测口服药物排放方面具有潜力,包括透性和第一通代谢.
- 类药物对评估药物诱导的胃肠道毒性和查治疗疗效有前途.
结论:
- 人体体系统代表了临床前药物开发的重大进步.
- 与传统系统相比,这些模型提供了比传统系统更好的肠道生物学概述.
- 需要进一步的研究,以充分阐明和优化体系统的应用.
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