化尼古拉胺乙醇胺在绵羊中的单剂量药理动力学和肺功能
Anne Weiss1,2, Robert J Bischof3,4,5, Cornelia B Landersdorfer5
1UNION therapeutics Research Services, Hellerup, Denmark.
Pharmaceutical research
|July 27, 2023
概括
与口服相比,直接输入肺部的雾化尼古拉胺 (尼古拉胺) 在肺液中的度显著更高. 这种新的输送途径为灵毒药提供了改善的肺部暴露.
科学领域:
- 药理学 药理学是指药理学的学科.
- 药物输送系统 药物输送系统
- 肺部医学 肺部医学
背景情况:
- 尼克洛萨米德是一种口服甲虫药物,由于口服生物可用性差,具有有限的医疗效用.
- 高度的药物通常需要在胃肠道以外的治疗疗效.
- 一种新型的尼克洛萨米德乙醇胺盐溶液已被开发用于雾化和鼻内输送.
研究的目的:
- 为了研究和比较尼古拉胺通过静脉,口服和雾化给药途径的肺部暴露.
- 在绵羊模型中表征化尼古洛萨米德上升剂量的血和肺药理动力学.
- 评估雾化尼古洛萨米德的安全性和耐受性,包括肺功能测试.
主要方法:
- 在羊群中单剂量使用后,尼古洛萨米德在血和上皮层内膜液 (ELF) 中的药理动力学分析.
- 雾化尼古拉胺的药理动力学与静脉注射的尼古拉胺进行区间建模的比较.
- 对肺部暴露的评估相对于尼古洛萨米德的批准口服剂量相当于人类的评估.
主要成果:
- 在所有测试剂量中,雾化尼古洛萨米德耐受性良好,对肺功能没有不良影响.
- 雾化尼古拉胺的血药理动力学表明剂量线性和绝对生物利用率为86%.
- 与口服相比,雾化尼古洛萨米德达到578倍高的ELF峰值度和71倍高的AUC.
结论:
- 尼克洛萨米德通过雾化进行局部肺部注射是安全的,并且在绵羊中耐受良好.
- 雾化显著增加了肺部尼古洛萨米德的暴露,达到比口服输送高得多的ELF度.
- 这种优化的输送方法有望提高尼古洛萨米德在肺部相关应用中的治疗潜力.
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