皮下用齐卢科普兰:对生殖毒理学的评估
Marie Lemper1, C Marc Luetjens2, Antje Fuchs2
1UCB, Cambridge, MA, USA.
Reproductive toxicology (Elmsford, N.Y.)
|March 6, 2025
概括
对非人类灵长类动物的生殖毒理学研究表明,齐卢科普兰对男性生育能力或胚胎发育没有不良影响. 齐卢科普兰显示出较低的胎盘转移率,这表明怀孕期间的风险很小.
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
- 生殖科学 生殖科学
背景情况:
- 了解齐卢科普兰的安全性对其临床应用至关重要.
- 生殖和发育毒性评估是药物安全性评估的重要组成部分.
研究的目的:
- 评估齐卢科普兰在非人类灵长类动物 (NHPs) 的生殖毒理学.
- 评估齐卢科普兰对男性生育能力,胚胎胎发育 (EFD) 和增强产前和产后发育 (ePPND) 的潜在影响.
- 为了检查 zilucoplan 在 ex vivo 人类胎盘 perfusion 模型中的胎盘转移.
主要方法:
- 在Cynomolgus子中进行了雄性生育研究和联合EFD/ePPND研究,每天用皮下注射zilucoplan.
- 使用了ex vivo人类胎盘 perfusion 模型来量化 zilucoplan 通过胎盘传输.
- 分析了发育性,生殖性和毒动力学影响.
主要成果:
- 没有观察到与兹卢科普兰相关的对男性生育能力的不良影响.
- 在EFD/ePPND研究中,没有发现对妊娠结果,可活胎儿或胎儿发育有重大影响.
- 接受齐卢科普兰治疗的群体的妊娠流产率与对照组相比较,并且在Cynomolgus子的预期范围内.
- 外体活体胎盘转移研究表明,齐卢科普兰的转移率低 (0.5%).
结论:
- 齐卢科普兰不会对男性生育能力,母亲健康或胚胎胎和产前/产后发育产生不良影响.
- 观察到的较低的胎盘转移表明胎儿暴露于zilucoplan的风险有限.
- 这些发现支持齐卢科普兰在生殖和发育毒性方面的安全性.
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