PopPK模型支持儿童的BW频段剂量
Yue Li1, Hong-Li Guo1, Lin Fan1
1Pharmaceutical Sciences Research Center, Department of Pharmacy, Children's Hospital of Nanjing Medical University, Nanjing, China.
NPJ genomic medicine
|August 28, 2025
概括
现在可以为患有的儿童简化lacosamide (LCM) 的剂量. 群体药动力学模型显示,体重范围或固定的剂量达到与基于体重的剂量相似的结果,改善了个性化治疗.
科学领域:
- 药理学
- 儿童
- 临床药房
背景情况:
- 对抗药物的个性化精确剂量是一个重大的临床挑战.
- 在儿科中使用的乳胺 (LCM) 剂量通常取决于体重 (BW) 的 (mg/ kg) 方案.
- 优化LCM剂量方案可以改善治疗结果和患者管理.
研究的目的:
- 评估从基于体重 (BW) 的 (mg/kg) 到简化的BW-band或固定剂量 (mg) 治疗方案的乳胺 (LCM) 剂量转换.
- 评估基因型导向剂量模型与基于BW模型的预测性能.
- 在不同剂量策略中确认可比的LCM暴露和目标达到.
主要方法:
- 使用非线性混合效应模型对190名儿科患者的现实数据进行群体药动力学 (PopPK) 建模.
- 基于BW的标准模型 (I模型) 与基因型导向模型 (II模型) 的比较.
- 蒙特卡洛模拟以评估各种剂量方案的LCM暴露和目标达到,包括BW频段和固定的剂量策略.
主要成果:
- 基因型导向模型 (模型II) 显示出优异的预测性能.
- 蒙特卡洛模拟证实了不同剂量方案中的可比性lacosamide (LCM) 暴露.
- 在外部验证中实现了78%的目标.
- 对于体重≥10公斤的患者,固定的100毫克剂量与体重调整后的剂量相等,在不同年龄组 (1-4岁) 和肥胖患者中一致.
结论:
- 在儿童中,用体重 (BW) 范围给药是一种临床上可行的,简化的替代方案.
- 基因定型进一步提高了剂量准确性,支持个性化的治疗.
- 这种基于人群药理学 (PopPK) 的策略简化了LCM治疗而不影响疗效,为儿童治疗提供了一种实用方法.
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