关于咖啡因作为单克隆抗体配方辅料的临床前药理动力学研究
Yuhong Zeng1, Subhashchandra Naik1, Timothy Tran1
1Comera Life Sciences, Inc., 12 Gill Street Suite 4650, Woburn, MA 01801, USA.
Journal of pharmaceutical sciences
|July 30, 2023
概括
咖啡因有效地降低了用于皮下输送的高度单克隆抗体 (mAb) 配方中的粘度. 临床前研究表明,咖啡因具有快速的药理动力学,并且不会影响mAb概况,支持其作为新型辅助剂的发展.
科学领域:
- 药理学 药理学是指药理学的学科.
- 生物技术是生物技术.
- 药物运输 药物运输 药物运输
背景情况:
- 高度单克隆抗体 (mAb) 配方由于高粘度而对皮下 (SQ) 输送具有挑战性.
- 需要新的辅助剂来改善这些生物制剂的注射性和输送.
- 咖啡因已经成为一种潜在的粘度降低剂.
研究的目的:
- 为了评估咖啡因的药理动力学 (PK) 参数,当施用SQ.
- 评估咖啡因对大鼠模型mAb (ipilimumab) 的PK概况的影响.
- 为了确定SQ咖啡因注射的安全性和耐受性.
主要方法:
- 在老鼠身上进行了两项临床前研究.
- 在SQ给药后,测量了咖啡因和伊皮利木马布的药理学参数 (Tmax,T1/2,生物可用性).
- 进行了组织病理学检查,以评估注射部位的刺激.
主要成果:
- 咖啡因呈现出快速的SQ吸收和排泄 (Tmax~0.4小时,T1/2~1.6小时),而不管与伊皮利马布同时服用.
- 咖啡因没有改变ipilimumab的SQ PK概况;血清T1/2为2-3天,Tmax为3-4天,生物利用率为~64%.
- 在不同剂量的SQ咖啡因下,没有观察到注射部位刺激或不良反应.
结论:
- 咖啡因表现出有利的PK特性,并且可以很好地容忍SQ注射.
- 咖啡因不会干扰单克隆抗体的PK,验证了其作为减少粘度的辅助剂的潜力.
- 对mAb SQ配方的咖啡因进一步开发是有必要的.
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