Covance Laboratories Ltd., Harrogate, UK.
Novo Nordisk A/S, Novo Nordisk Park, Denmark.
J Pharmacol Toxicol Methods. 2021 Jan-Feb;107:106947. doi: 10.1016/j.vascn.2020.106947. Epub 2021 Jan 9.
Understanding the absorption, distribution, metabolism and excretion (ADME) of candidate drugs in preclinical species is an integral part of the safety and efficacy evaluation in drug development. For this purpose, the housing of single animals in metabolism cages has historically been common practice for ADME studies. Whilst mini-pigs and dogs are selected wherever possible, non-human primates (NHPs) are used where there is no suitable scientific alternative. Having undergone only minimal revisions over the past 30 years, the traditional single-housing metabolism cage design for NHPs significantly limits normal vertical movement and social behaviours in primates. Minimising animal suffering and improving welfare is an important aspect of working with animals in research and Novo Nordisk A/S, together with collaborators, has focused on this area for many years. A novel metabolism cage for group housing of NHPs has been designed in a joint collaboration between Novo Nordisk A/S and Covance Inc. The advantages of this novel cage are extensive, including a significantly increased cage volume and ability for socialisation, as well as improvements to alleviate stress and boredom. The excretion balance data from six male NHPs housed in single or group metabolism cages were compared using the radiolabelled test compound [C]-quetiapine. Welfare, in terms of stress and behaviour, when animals were single or group housed was also assessed. Mean recoveries of radioactivity were shown to be comparable irrespective of housing design (83.2% for group-housed animals vs. 87.1% for single-housed animals), supporting the potential suitability of NHP group housing for future metabolism ADME studies.
了解候选药物在临床前物种中的吸收、分布、代谢和排泄(ADME)是药物开发中安全性和功效评估的一个组成部分。为此,历史上在 ADME 研究中,将单个动物饲养在代谢笼中是常见的做法。虽然尽可能选择小型猪和狗,但在没有合适的科学替代方案时,会使用非人类灵长类动物(NHPs)。传统的用于 NHP 的单笼代谢笼设计在过去 30 年中仅进行了最小的修订,这极大地限制了灵长类动物的正常垂直运动和社交行为。减轻动物的痛苦和改善福利是动物研究中的一个重要方面,诺和诺德公司及其合作者多年来一直专注于这一领域。诺和诺德公司与 Covance Inc. 合作设计了一种用于 NHPs 群体饲养的新型代谢笼。这种新型笼具具有许多优点,包括笼子体积显著增加和能够进行社交,以及减轻压力和无聊的改进。使用放射性标记的测试化合物 [C]-喹硫平比较了单独或群体饲养在单个或群体代谢笼中的六只雄性 NHP 的排泄平衡数据。还评估了动物单独或群体饲养时的福利(压力和行为方面)。无论饲养设计如何,放射性回收率均显示出相当(群体饲养动物为 83.2%,单独饲养动物为 87.1%),支持未来代谢 ADME 研究中 NHPs 群体饲养的潜在适用性。