Hurel Corporation, Beverley Hills, CA, USA.
Curr Drug Metab. 2009 Dec;10(10):1192-9. doi: 10.2174/138920009790820093.
One of the fundamental challenges facing the development of new chemical entities within the pharmaceutical industry is the extrapolation of key in vivo parameters from in vitro cell culture assays and animal studies. Development of microscale devices and screening assays incorporating primary human cells can potentially provide better, faster and more efficient prediction of in vivo toxicity and clinical drug performance. With this goal in mind, large strides have been made in the area of microfluidics to provide in vitro surrogates that are designed to mimic the physiological architecture and dynamics. More recent advancements have been made in the development of in vitro analogues to physiologically-based pharmacokinetic (PBPK) models - a mathematical model that represents the body as interconnected compartments specific for a particular organ. In this review we highlight recent advancements in human hepatocyte microscale culture, and describe the next generation of integrated devices, whose potential allows for the high throughput assessment of drug metabolism, distribution and pharmacokinetics.
制药行业开发新化学实体面临的一个基本挑战是，如何将关键的体内参数从体外细胞培养测定和动物研究中推断出来。开发包含原代人细胞的微尺度装置和筛选测定法，有可能提供更好、更快和更有效的体内毒性和临床药物性能预测。有鉴于此，在微流控领域已经取得了很大的进展，提供了旨在模拟生理结构和动态的体外替代物。在开发基于生理的药代动力学（PBPK）模型的体外类似物方面也取得了一些最新进展——这是一种数学模型，将身体表示为特定器官特有的相互连接的隔室。在这篇综述中，我们重点介绍了人肝细胞微尺度培养的最新进展，并描述了下一代集成设备，其潜力允许高通量评估药物代谢、分布和药代动力学。
