患有中度至重度活性的性结肠炎的患者中的米里基祖马布的药理动力学:来自III期LUCENT研究的结果
Laiyi Chua1, Stuart Friedrich1, Xin Cindy Zhang2
1Global PK/PD and Pharmacometrics, Eli Lilly and Company, 893 Delaware Street, Indianapolis, IN, 46225, USA.
Clinical pharmacokinetics
|August 23, 2023
概括
在性结肠炎患者的Mirikizumab药理动力学显示出典型的单克隆抗体特征. 尽管体重和白蛋白对清除的轻微影响,但不需要调整剂量.
科学领域:
- 药理学 药理学是指药理学的学科.
- 免疫学 免疫学 免疫学
- 胃肠病学 胃肠病学
背景情况:
- 米里基祖马布是一种抗联素-23-p19单克隆抗体.
- 它正在开发用于性结肠炎和克罗恩病.
- 这项研究重点研究了mirikizumab在性结肠炎患者中的药理动力学.
研究的目的:
- 为了描述mirikizumab的药理动力学.
- 评估共变量对米里基祖马布暴露的影响.
- 为了告知mirikizumab在性结肠炎中的剂量策略.
主要方法:
- 来自II期和III期试验的药理动力学数据的分析 (N=1362).
- 使用非线性混合效应建模用于药理动力学表征.
- 使用基于模拟的估计来评估共变量效应.
主要成果:
- 米里基祖马布的药理动力学遵循一个线性两模型.
- 关键参数包括清除值 (0.022 L/h),分布量 (3.11 L和1.69 L) 和半衰期 (9.5 天).
- 体重,白蛋白和BMI对暴露有轻微影响;皮下生物利用率为48%.
结论:
- 米里基祖马布表现出典型的单克隆抗体的药理动力学特性.
- 轻微的共变效应表明,不需要对患者因素进行剂量调整.
- 这些发现支持了mirikizumab在性结肠炎中的确定的剂量方案.
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