当前位置: X-MOL 学术Annu. Rev. Pharmacol. Toxicol. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Physiologically Based Pharmacokinetic and Pharmacodynamic Analysis Enabled by Microfluidically Linked Organs-on-Chips
Annual Review of Pharmacology and Toxicology ( IF 12.5 ) Pub Date : 2018-01-08 00:00:00 , DOI: 10.1146/annurev-pharmtox-010716-104748
Rachelle Prantil-Baun 1 , Richard Novak 1 , Debarun Das 2 , Mahadevabharath R. Somayaji 2 , Andrzej Przekwas 2 , Donald E. Ingber 1, 3, 4
Affiliation  

Physiologically based pharmacokinetic (PBPK) modeling and simulation approaches are beginning to be integrated into drug development and approval processes because they enable key pharmacokinetic (PK) parameters to be predicted from in vitro data. However, these approaches are hampered by many limitations, including an inability to incorporate organ-specific differentials in drug clearance, distribution, and absorption that result from differences in cell uptake, transport, and metabolism. Moreover, such approaches are generally unable to provide insight into pharmacodynamic (PD) parameters. Recent development of microfluidic Organ-on-a-Chip (Organ Chip) cell culture devices that recapitulate tissue-tissue interfaces, vascular perfusion, and organ-level functionality offer the ability to overcome these limitations when multiple Organ Chips are linked via their endothelium-lined vascular channels. Here, we discuss successes and challenges in the use of existing culture models and vascularized Organ Chips for PBPK and PD modeling of human drug responses, as well as in vitro to in vivo extrapolation (IVIVE) of these results, and how these approaches might advance drug development and regulatory review processes in the future.

中文翻译:


微流控芯片对芯片的生理基础药代动力学和药效学分析

基于生理的药代动力学(PBPK)建模和模拟方法已开始集成到药物开发和批准过程中,因为它们使关键的药代动力学(PK)参数能够从体外数据中预测出来。但是,这些方法受到许多限制的束缚,包括无法纳入因细胞吸收,转运和代谢差异而导致的器官特异性差异,从而导致药物清除,分布和吸收方面的差异。而且,这些方法通常不能提供对药效学(PD)参数的了解。微流控芯片上器官(Organ Chip)细胞培养设备的最新进展,概述了组织与组织之间的界面,血管灌注,当多个器官芯片通过其内衬血管的血管通道相连时,器官级功能可以克服这些限制。在这里,我们讨论使用现有的培养模型和血管化器官芯片对人药反应进行PBPK和PD建模的成功与挑战,以及这些结果的体外到体内外推(IVIVE),以及这些方法如何发展未来的药物开发和法规审查程序。

更新日期:2018-01-08
down
wechat
bug