Morgan Sherry J, Elangbam Chandikumar S, Berens Shawn, Janovitz Evan, Vitsky Allison, Zabka Tanja, Conour Laura
Abbott Laboratories, Preclinical Safety, Abbott Park, IL 60064, USA.
Toxicol Pathol. 2013;41(3):508-18. doi: 10.1177/0192623312457273. Epub 2012 Sep 11.
Animal models of human disease are commonly utilized to gain insight into the potential efficacy and mode of action of novel pharmaceuticals. However, conventional (healthy) rodent and nonrodent models are generally utilized in nonclinical safety testing. Animal models of human disease may be helpful in understanding safety risks of compounds in nonclinical or clinical development, with their greatest value being in targeted or hypothesis-driven studies to help understand the mechanism of a particular toxicity. Limitations of animal models of disease in nonclinical safety testing include a lack of historical control, heterogeneity in disease expression, a limited life span, and confounding effects of the disease. In most instances, animal models of human disease should not be utilized to supplant testing in conventional animal models. While of potential benefit, testing in an animal model of human disease should only be taken after adequate consideration of relevance along with benefits and limitations of the proposed model.
人类疾病动物模型通常用于深入了解新型药物的潜在疗效和作用方式。然而，传统的（健康）啮齿动物和非啮齿动物模型一般用于非临床安全性测试。人类疾病动物模型可能有助于了解化合物在非临床或临床开发中的安全风险，其最大价值在于针对性或假设驱动的研究，以帮助理解特定毒性的机制。非临床安全性测试中疾病动物模型的局限性包括缺乏历史对照、疾病表达的异质性、有限的寿命以及疾病的混杂效应。在大多数情况下，人类疾病动物模型不应被用于替代传统动物模型的测试。虽然有潜在益处，但在人类疾病动物模型中进行测试应在充分考虑相关性以及所提议模型的益处和局限性之后再进行。
