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人口药理动力学模型的外部评估在双极人群中的
Lereclus Aurélie1,2, Boniffay Andréa2, Kallée Gauvind3
1Institut de Neurosciences des Systèmes, Aix Marseille Université, Inserm UMR 1106, 13385 Marseille, France.
Pharmaceuticals (Basel, Switzerland)
|November 25, 2023
概括
大多数的人口药理动力学 (popPK) 模型在治疗双相情感障碍时显示出较差的预测性表现. 以状况等因素来改进这些模型对于个性化剂量策略至关重要.
科学领域:
- 药理动力学和药理动力学
- 临床药理学 临床药理学
- 双极性障碍的治疗方法
背景情况:
- 是双相情感障碍治疗的基石,但其狭窄的治疗指数和可变的药理动力学 (PK) 需要剂量优化.
- 种群药动力学 (popPK) 模型旨在预测个人剂量,帮助个性化治疗.
- 评估现有的popPK模型的临床实用性对于可靠的治疗药物监测至关重要.
研究的目的:
- 用两个独立的外部数据集来评估已发布的popPK模型的预测性能.
- 识别影响模型可预测性的因素,并比较不同数据集的性能.
- 确定目前用于剂量的popPK模型的临床适用性.
主要方法:
- 系统地识别可用的popPK模型.
- 使用临床数据集 (46名患者) 和文献数据集 (89名患者) 对选定的模型进行外部验证.
- 评估预测误差 (PE) 和中位数绝对PE以量化偏差和不准确性.
主要成果:
- 在评估的popPK模型中,只有一个在两个数据集中满足了可接受性标准.
- 大多数模型显示出显著的偏差和不准确性,中位数PE在-6.6%至111.2%之间,中位数绝对PE在24.4%至111.2%.
- 在模型开发中对关键的共同变量 (如状况) 的有限纳入导致了可预测性差.
结论:
- 现有的popPK模型具有有限的预测性能,阻碍其用于精确剂量的临床应用.
- 在模型结构中缺少关键共变量,如功能,是主要的局限性.
- 通过使用诸如元建模等方法来改进popPK模型,并结合相关的共变量,对于在治疗中推进基于模型的精确剂量至关重要.
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