在患有固体瘤的患者中对Adavosertib (AZD1775) 的人口药动力学建模
Martin Johnson1, Daniel Kaschek2, Dana Ghiorghiu3
1Clinical Pharmacology and Quantitative Pharmacology, Clinical Pharmacology and Safety Science, R&D, AstraZeneca, Cambridge, UK.
阿达沃谢蒂布 (AZD1775),是一种Wee1激酶抑制剂,在固体瘤患者中显示出可变的药物暴露. 体重,功能障碍和种族显著影响阿达沃谢蒂布暴露水平.
科学领域:
- 药理学 药理学是指药理学的学科.
- 在瘤学瘤学.
- 临床药理学 临床药理学
背景情况:
- 阿达沃谢蒂布 (AZD1775) 是一种强大的小分子抑制剂,向Wee1激酶.
- 微1激酶在细胞循环调节和DNA损伤反应中起着至关重要的作用,使其成为癌症治疗的目标.
研究的目的:
- 在有固体瘤的患者中表征阿达沃谢蒂布的种群药理学.
- 评估各种共同变量对阿达沃谢蒂布暴露指标的影响.
主要方法:
- 利用了来自8项I/II期研究的药理动力学数据,这些研究涉及538名患有固体瘤的患者.
- 采用非线性混合效应建模方法来估计群体和个体药理动力学参数.
- 使用视觉预测检查 (VPC) 和稳定状态观测验证了最终模型.
主要成果:
- 一个具有时间变化的清除的线性2区模型最好地描述了Adavosertib的药理动力学.
- 模拟分析确定了体重,功能障碍状态和种族作为影响药物暴露的关键共变量.
- 该模型在模拟不同患者群体方面表现出可靠性.
结论:
- 种群药动力学建模为了解阿达沃谢蒂布暴露提供了一个强大的框架.
- 阿达沃谢蒂布的剂量可能需要根据个体患者的特征进行调整,例如体重,功能和种族.
- 这些发现支持在固体瘤治疗中针对阿达沃谢蒂布的个性化剂量策略.
更多相关视频
09:29Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies
Published on: September 30, 2016
10:27Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts
Published on: July 25, 2020
相关概念视频
Analysis of Population Pharmacokinetic Data
Model Approaches for Pharmacokinetic Data: Distributed Parameter Models
The distributed parameter models are specifically designed to account for variations and differences in some drug classes. This model is particularly useful for assessing regional concentrations of anticancer or...
Model Approaches for Pharmacokinetic Data: Compartment Models
Two primary types of compartment models are recognized: mammillary and catenary. The more...
Pharmacokinetic Models: Overview
There are three primary types of models: empirical, compartment, and physiological. Empirical models, with minimal...
Physiological Pharmacokinetic Models: Incorporating Hepatic Transporter-Mediated Clearance
A recent model describes pravastatin's hepatobiliary excretion,...
Analysis Methods of Pharmacokinetic Data: Model and Model-Independent Approaches
The model approach uses mathematical models to describe changes in drug concentration over time. Pharmacokinetic models help characterize drug behavior in patients, predict drug concentration in the body fluids, calculate optimum dosage regimens, and evaluate the risk of toxicity. However, ensuring that the model fits the experimental data accurately...
