在健康受试者中预测纳多洛尔血度-时间曲线下的区域的有限采样策略
Shingen Misaka1, Yuko Maejima1, Kenju Shimomura1
1Department of Bioregulation and Pharmacological Medicine, Fukushima Medical University School of Medicine, Fukushima, Japan.
Journal of clinical pharmacology
|November 17, 2024
概括
这项研究开发了可靠的有限采样策略 (LSS) 模型来预测纳多洛尔.
科学领域:
- 药理动力学和药物新陈代谢
- 载体介导的药物相互作用
背景情况:
- 纳多洛尔 (nadolol) 是一种性β-阻断剂,是P-糖蛋白和OATP1A2.2.的基质.
- 这些载体参与药物-药物和食物-药物相互作用.
- 评估这些相互作用对于安全有效的药物治疗至关重要.
研究的目的:
- 开发和验证有限采样策略 (LSS) 模型,用于预测纳多洛的血度-时间曲线 (AUC) 下的面积.
- 评估这些LSS模型在预测纳多洛尔药理动学的可靠性,包括在药物相互作用研究期间.
主要方法:
- 来自健康志愿者的血度数据被用来开发多重线性回归模型.
- 模型是使用nadolol度的两个和三个时间点来开发的.
- 使用培训和测试数据集评估模型性能,并在药物相互作用研究中验证.
主要成果:
- 三个时间点LSS模型显示出高预测性能 (r2值为0.983和0.980).
- LSS模型准确地预测了nadolol在与伊特拉科纳,利芬素,葡萄汁和绿茶提取物相互作用期间的AUC.
- 模型显示低预测误差 (MAE ≤11%,RMSE ≤12%) 并在不同的剂量中得到验证.
结论:
- 使用三个时间点的有限采样策略模型提供了一种可靠的方法来预测健康人群中nadolol的曲线下面积 (AUC).
- 这些LSS模型是药理动力学评估和涉及nadolol的药物相互作用研究的宝贵工具.
- 开发的模型可以帮助优化纳多洛尔剂量,并了解其与其他物质的相互作用.
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