Centre for Biological Engineering, Department of Chemical Engineering, Loughborough University, Loughborough LE11 3TU, UK.
Drug Discov Today. 2013 Oct;18(19-20):922-35. doi: 10.1016/j.drudis.2013.05.016. Epub 2013 Jun 5.
Bringing a new drug to market is costly in terms of capital and time investments, and any development issues encountered during late-stage clinical trials can often be the result of in vitro-in vivo extrapolations (IVIVE) not accurately reflecting clinical outcome. In the discipline of drug metabolism and pharmacokinetics (DMPK), current in vitro cellular methods do not provide the 3D structure and function of organs found in vivo; therefore, new dynamic methods need to be established to aid improvement of IVIVE. In this review, we highlight the importance of model progression into dynamic systems for use within drug development, focusing on devices developed currently in the areas of the liver and blood-brain barrier (BBB), and the potential to develop models for other organ systems, such as the kidney. We discuss the development of dynamic 3D bioreactor-based systems as in vitro models for use in DMPK studies.
将一种新药推向市场需要在资本和时间上投入大量资金，而在后期临床试验中遇到的任何开发问题通常都可能是由于体外-体内外推（IVIVE）不能准确反映临床结果所致。在药物代谢和药代动力学（DMPK）领域，当前的体外细胞方法不能提供体内发现的器官的 3D 结构和功能；因此，需要建立新的动态方法来帮助改进 IVIVE。在这篇综述中，我们强调了将模型推进到用于药物开发的动态系统中的重要性，重点介绍了目前在肝脏和血脑屏障（BBB）领域开发的设备，以及为其他器官系统（如肾脏）开发模型的潜力。我们讨论了基于动态 3D 生物反应器的系统作为用于 DMPK 研究的体外模型的发展。
