使用现实世界的数据来外部评估儿童和婴儿中德克斯梅德托米丁的人口药动力学模型
Sean McCann1, Victória E Helfer1, Stephen J Balevic2,3
1Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Journal of clinical pharmacology
|March 28, 2024
概括
在儿童中对德克斯梅德托米丁药物动力学模型的外部验证显示了显著的变异性. 詹姆斯和其他人. 模型显示出对现实世界的剂量有希望,尽管存在局限性.
科学领域:
- 药理学 药理学是指药理学的学科.
- 儿科医学 儿科医学
- 药物开发 药物开发
背景情况:
- 德克斯梅德托米丁是一种广泛使用的镇静剂,在儿科患者群体中具有显著的个人间药理动力学变异性.
- 现有的儿童用德克斯梅德托米丁的种群药动力学 (PK) 模型需要外部验证,以评估它们在现实世界中的适用性.
- 了解PK的变异性对于优化儿科患者的德克斯梅德托米丁剂量至关重要.
研究的目的:
- 在儿科队列中对德克斯梅德托米丁的五个已发表的人口PK模型进行外部验证.
- 通过使用前性,机会性PK数据集来评估这些模型的概括性和准确性.
- 确定最可靠的模型,以告知儿童用德克斯梅德米丁的剂量.
主要方法:
- 从102名儿童和年轻成年人 (0.01-19.9岁) 收集了前性PK数据集.
- 五个已发表的德克斯梅德托米丁PK模型被选择用于外部验证.
- 使用NONMEM和R进行了定量和视觉分析,以比较观察到的度与人口 (PRED) 和个性化 (IPRED) 预测.
主要成果:
- 预测误差的平均百分比在各种模型中差异很大,从PRED的-1%到120%,从IPRED的-24%到60%.
- 詹姆斯等人的模型. 显示出最佳表现,几乎符合IPRED预测的概括性标准.
- 从临床试验数据开发的模型在应用于更多样化,现实世界的数据集时显示出局限性.
结论:
- 在儿童中对德克斯梅德托米丁PK模型的外部验证突出显示了显著的预测错误和可变性.
- 詹姆斯和其他人. 该模型显示,尽管存在局限性,但在住院儿童中基于模型的剂量可能具有潜在的实用性.
- 需要进一步的细化和验证,以确保在多样化的儿科群体中准确和安全的德克斯梅德托米丁剂量.
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