Davis T Gregg
Boehringer Ingelheim Pharmaceuticals Inc, Ridgefield, Connecticut.
Curr Protoc Neurosci. 2016 Oct 3;77:9.53.1-9.53.6. doi: 10.1002/cpns.12.
The ability to assess the potential for gastrointestinal adverse events in a preclinical setting is a challenge in the development of new drugs, as the vast majority of in vivo research is conducted in rodent species lacking a vomiting reflex. The use of higher species capable of emesis is often limited by cost, technical experience, and relevant efficacy models to define a therapeutic index. Additionally, investigators should be mindful of ethical considerations when using more sentient species when an alternative in lower species is available. This unit describes the use of pica behavior in rodents as an alternative for evaluating emetic potential in vivo. After an acclimation period, the incidence of rats engaging in pica following the administration of a test article can be used to generate a dose-response curve of the pica behavior. When linked with an appropriate efficacy model, this allows compounds to be ranked based on therapeutic index. © 2016 by John Wiley & Sons, Inc.
在临床前环境中评估胃肠道不良事件可能性的能力，是新药研发中的一项挑战，因为绝大多数体内研究是在缺乏呕吐反射的啮齿类动物中进行的。使用能够呕吐的高等物种往往受到成本、技术经验以及用于定义治疗指数的相关药效模型的限制。此外，当有低等物种的替代方案时，研究人员在使用更具感知能力的物种时应考虑伦理因素。本单元描述了将啮齿类动物的异食癖行为作为评估体内催吐潜力的一种替代方法。在适应期后，给予受试物后出现异食癖的大鼠发生率可用于生成异食癖行为的剂量 - 反应曲线。当与适当的药效模型相结合时，这使得化合物能够根据治疗指数进行排名。© 2016 约翰威立国际出版公司
