Ishida Seiichi
Division of Pharmacology, National Institute of Health Sciences, Japan.
Drug Metab Pharmacokinet. 2018 Feb;33(1):49-54. doi: 10.1016/j.dmpk.2018.01.003. Epub 2018 Jan 11.
Assay systems using in vitro cultured cells are increasingly applied for evaluation of the efficacy, safety, and toxicity of drug candidates. In vitro cell-based assays have two main applications in the drug discovery process: searching for a compound that is effective against the target disease (seed investigation) and confirmation of safety during use of the identified compounds (safety assessment). Currently available in vitro cell-based assays have been designed to evaluate the efficacy and toxicity in single organs, but the in vivo pharmacokinetics and pharmacodynamics of the administered drug candidates have not been considered. Thus, an evaluation system that interconnects cell culture units, one of which has appropriate drug metabolism activities and the other assesses the efficacy and toxicity of compounds, is needed. Accordingly, the in vitro ADME-Tox culture system known as organs-on-a-chip has been proposed. In this review, after introducing the organs-on-a-chip system, the evaluation of enterohepatic circulation and the gut-liver axis relationship will be presented as an example of the application of the organs-on-a-chip system for ADME studies based on inter-organ network. Additionally, the functions required for the organs-on-a-chip system and the necessity of standardization of cells mounted on the chip system will be discussed.
使用体外培养细胞的检测系统越来越多地用于评估候选药物的疗效、安全性和毒性。基于体外细胞的检测在药物发现过程中有两个主要应用：寻找对目标疾病有效的化合物（种子研究）以及确认已鉴定化合物在使用过程中的安全性（安全性评估）。目前可用的基于体外细胞的检测旨在评估单一器官中的疗效和毒性，但尚未考虑所给药候选药物的体内药代动力学和药效学。因此，需要一种将细胞培养单元相互连接的评估系统，其中一个具有适当的药物代谢活性，另一个评估化合物的疗效和毒性。相应地，已经提出了被称为芯片上器官的体外ADME-Tox培养系统。在这篇综述中，在介绍芯片上器官系统之后，将以肠肝循环和肠-肝轴关系的评估为例，介绍芯片上器官系统在基于器官间网络的ADME研究中的应用。此外，还将讨论芯片上器官系统所需的功能以及芯片系统上所安装细胞标准化的必要性。
