胃肠综合体的最新进展 在ADME研究的体外模型中
Kazuyoshi Michiba1, Kengo Watanabe1, Tomoki Imaoka1
1Drug Metabolism & Pharmacokinetics Research Laboratory, Daiichi Sankyo Co., Ltd., 1-2-58, Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.
Pharmaceutics
|January 23, 2024
概括
使用人类肠道器官的复杂体外模型 (CIVMs) 提供了比传统方法更准确的研究药物吸收的方法. 这些先进的模型更好地代表了药物发现和开发的人类肠道.
科学领域:
- 药理学 药理学是指药理学的学科.
- 药物代谢和药理动力学
- 胃肠病学 胃肠病学
背景情况:
- 肠道吸收对药物的有效性至关重要,受到屏障透性,转运体活性和新陈代谢的影响.
- 传统的体外模型,如Caco-2单层和Ussing腔,在预测人类肠道药物吸收方面存在局限性.
- 准确预测药物吸收需要强大的体外系统来模仿人类肠道环境.
研究的目的:
- 审查复杂的体外模型 (CIVMs) 的最新进展,以研究肠道药物吸收.
- 为了比较新型肠道CIVM与常规体外方法的实用性.
- 突出CIVM在药物发现和开发中的潜力.
主要方法:
- 对肠道复合体体外模型 (CIVMs) 的最新文献的审查.
- 专注于在微生理系统中利用人类肠道有机体和iPSC衍生的肠细胞的模型.
- 将CIVM与传统的Caco-2和Ussing室模型进行比较.
主要成果:
- 复杂的体外模型 (CIVM) 与传统方法相比,显示出更强大的生理相关性.
- CIVM,特别是使用肠道有机体的CIVM,更好地复制关键ADME相关蛋白质的表达和功能.
- 这些先进的模型有望改善对人类药物吸收的预测.
结论:
- 复杂的体外模型 (CIVMs) 与研究肠道吸收的传统方法相比,是一个显著的进步.
- 基于肠道有机体的CIVMs为药物发现和开发提供了更具预测性的平台.
- 选择和定制CIVM应该基于特定的药物特性和研究目标.
相关概念视频
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01:09Methods for Studying Drug Absorption: In situ
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In situ experiments, such as the Doluisio method and Single-Pass Perfusion technique, provide critical insights into drug uptake by simulating in vivo conditions for drug absorption.
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