F. Hoffmann-La Roche Ltd., Pharma Research, 4070 Basel, Switzerland.
Adv Drug Deliv Rev. 2014 Apr;69-70:179-89. doi: 10.1016/j.addr.2013.12.005. Epub 2013 Dec 27.
The selection of drug candidates early in development has become increasingly important to minimize the use of animals and to avoid costly failures of drugs later in development. In vitro systems to predict and assess organ toxicity have so far been of limited value due to difficulties in demonstrating in vivo-relevant toxicity at a cell culture level. To overcome the limitations of single-cell type monolayer cultures and short-lived primary cell preparations, researchers have created novel 3-dimensional culture systems which appear to more closely resemble in vivo biology. These could become a key for the pharmaceutical industry in the evaluation of drug candidates. However, the value and acceptance of those new models in standard drug safety applications have yet to be demonstrated. This review aims to provide an overview of the different approaches undertaken in the field of pre-clinical safety assessment, organ toxicity, in particular, with an emphasis on examples and technical challenges.
在药物开发的早期选择药物候选物对于减少动物的使用和避免药物在后期开发中的昂贵失败变得越来越重要。由于在细胞培养水平上难以证明与体内相关的毒性，因此预测和评估器官毒性的体外系统迄今为止价值有限。为了克服单细胞类型单层培养和寿命短的原代细胞制剂的局限性，研究人员创建了新型的 3 维培养系统，这些系统似乎更接近体内生物学。这些可能成为制药行业在评估药物候选物方面的关键。然而，这些新模型在标准药物安全性应用中的价值和接受程度仍有待证明。本综述旨在概述临床前安全性评估领域采用的不同方法，特别是器官毒性，重点介绍实例和技术挑战。
