基于综合临床I期和II期数据的elinzanetant的种群药动力学-药动力学模型
Stefan Willmann1, Adam Lloyd2, Rupert Austin2
1Bayer AG, Pharmaceuticals, Pharmacometrics/Modeling and Simulation, Wuppertal/Leverkusen/Berlin, Germany.
埃林扎内坦特有效地向经期血管运动症状 (VMS) 的神经激素-1 (NK-1) 和神经激素-3 (NK-3) 受体. 一种种群的药理动力学模型证实了它的安全性和有效性,在治疗剂量下显示了高受体占用率.
科学领域:
- 药理学 药理学是指药理学的学科.
- 临床药理学 临床药理学
- 妇女健康 妇女健康
背景情况:
- 埃林扎内坦是双重的神经素-1 (NK-1) 和神经素-3 (NK-3) 受体对手.
- 它正在开发用于与更年期相关的中度至严重的血管运动症状 (VMS).
研究的目的:
- 为了开发一个人群的药理动力学 (popPK) 模型为elinzanetant及其代谢物.
- 评估elinzanetant的药理动力学特性和受体占用率.
主要方法:
- 来自10项I/II期研究的综合数据,涉及366名受试者.
- 开发了一个popPK模型并将其与药理动力学模型相结合.
- 预测的NK-1和NK-3受体占用率.
主要成果:
- 这种popPK模型准确地描述了elinzanetant的药理动力学.
- 口服生物利用率是剂量独立的 (36.7%).
- 高脂肪的早餐影响了口服吸收;没有发现其他因素.
- 预测的NK-1和NK-3受体占用率中位数分别为>99%和>94.8%,每日剂量为120mg.
结论:
- 埃林扎尼坦特具有可预测的药理动力学.
- 每日120毫克的剂量可以实现NK-1和NK-3受体的持续,几乎完全的抑制.
- 这支持elalinzanetant在治疗更年期VMS方面的潜力.
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