用于临床前发作风险评估的实验室动物对药物诱导的发作的比较敏感性
Motohiro Shiotani1, Yuki Seki1, Misato Takano1
1Global Drug Safety, Biopharmaceutical Assessments Unit, Eisai Co., Ltd.
The Journal of toxicological sciences
|September 4, 2024
概括
药物诱导的风险评估在药物开发中至关重要. 这项研究发现,小鼠,大鼠和非人类灵长类动物 (NHPs) 对药物诱导的具有相似的敏感性,支持它们在临床前安全性评估中的使用.
科学领域:
- 药理学 药理学是指药理学的学科.
- 毒理学 毒理学 毒理学
- 药物开发 药物开发
背景情况:
- 药物诱导的是药物开发过程中的一个重大安全问题.
- 在临床前研究中评估候选药物的病责任是必不可少的.
- 有限的数据存在于对药物诱导的敏感度的物种间差异.
研究的目的:
- 为了比较小鼠,大鼠和非人类灵长类动物 (NHPs) 对药物诱导的的敏感性.
- 为了确定在发作的血药物度是否在这些物种之间有显著差异.
- 为了为临床前风险评估选择合适的动物模型提供信息.
主要方法:
- 来自各种药理类的11个试验物品被给予小鼠 (腹腔内) 和大鼠 (静脉注射).
- 还给了NHP (静脉输液) 六个测试物品.
- 测试物品的血度在发作时或服用后5分钟时被测量.
主要成果:
- 所有测试的物品都在小鼠和NHP中引起了,在11种产生的物品中,有10种在老鼠中引起了.
- 虽然老鼠和NHP有时表现出比小鼠更低度的,但度在物种之间通常是可比的 (差异为3倍).
- 在所有物种中都观察到的预示性迹象.
结论:
- 小鼠,老鼠和NHPs对药物诱导的发作具有相似的敏感性.
- 这些动物模型非常适合在药物开发早期评估风险.
- 模型选择可以基于诸如吞吐量,成本和特定药物要求等因素.
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