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一种用于Fc融合蛋白的人类药理动学的定量预测方法
Miki Yokoyama1, Eiko Suzuki2, Masataka Oitate2
1Drug Metabolism and Pharmacokinetics Research Laboratories, Daiichi Sankyo Co., Ltd., 1-2-58, Hiromachi, Shinagawa-ku, Tokyo, 140-8710, Japan. yokoyama.miki.mr@daiichisankyo.co.jp.
Fc融合技术延长了治疗性蛋白质的半衰期. 这项研究使用子数据成功预测了Fc融合蛋白的人类药理动力学,有助于药物开发.
科学领域:
- 药理动力学 药理动力学
- 生物技术是生物技术.
- 药物开发 药物开发
背景情况:
- Fc融合是一种经过验证的策略,可以延长治疗性蛋白质的半衰期.
- 延长蛋白质的半衰期对于有效的药物输送和剂量方案至关重要.
研究的目的:
- 评估Fc融合蛋白质的人类药理动力学预测方法.
- 为单克隆抗体 (mAbs) 开发的现有预测方法进行调整和扩展.
主要方法:
- 分析了子中的11种Fc融合蛋白的药理动力学数据,用于静脉注射 (IV),使用物种不变的时间和全米缩放.
- 通过从人类和子数据的剂量正常化和吸收参数分析 (生物可用性和吸收率常数) 预测皮下 (SC) 剂量配置.
主要成果:
- 该物种不变时间方法准确地预测了超过85%的Fc融合蛋白的IV剂量配置文件,在两倍的差异范围内.
- 对于SC剂量,使用mAbs和Fc融合蛋白质的人类吸收参数的几何介质,与简单的子数据规范化相比,提高了预测准确性.
结论:
- 通过使用子数据,成功预测了Fc融合蛋白 (IV和SC) 的人类药理动力学概况,精度达到两倍.
- 开发的预测方法对于加速药物发现和Fc融合蛋白的开发有价值.
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