开发和外部验证一个人群的药理动力学模型和最佳的万科米辛的剂量方案的超重和肥胖的患者的发展和外部验证
Toshiaki Komatsu1, Atsushi Tomizawa1, Masaru Samura2
1Department of Pharmacy, Kitasato University Hospital, 1-15-1 Kitasato, Minami-ku, Sagamihara-shi, Kanagawa, 252-0375, Japan.
概括
为超重和肥胖的成年人制定最佳的万科米辛剂量方案至关重要. 这种种群体的药理动力学模型准确地预测了使用肌素清除率和调整后的体重来预测米辛水平.
科学领域:
- 药理动力学 药理动力学
- 药学指标 (Pharmacometrics) 是一个指标.
- 内部医学 内部医学
背景情况:
- 在超重和肥胖的成年人中服用万科米辛剂量需要专门的模型.
- 现有的模型可能无法准确预测这些人群中的药物度.
研究的目的:
- 开发和验证Vancomycin的种群药动力学模型.
- 为超重和肥胖的成年人建立最佳的万科米辛剂量方案.
主要方法:
- 使用非线性混合效应建模,开发了一种两部分人群的药理动力学模型.
- 来自184名参与者的数据用于模型构建,对21名额外的参与者进行了外部验证.
- 蒙特卡洛模拟确定了400600μg·h/mL曲线下的目标稳定状态区域 (AUC) 的剂量.
主要成果:
- 范科米辛清除受到肌素清除 (CCr),血尿素 (BUN) 和心力衰竭发病率的显著影响.
- 调整后的体重 (AdjBW) 是分布体积的一个关键预测指标.
- 在外部验证中,与之前的模型相比,开发的模型表现出优异的预测性能.
结论:
- 在超重和肥胖患者中有效的万科米辛剂量取决于CCr,AdjBW,BUN水平和心力衰竭状态.
- 经过验证的模型为这些患者群体的优化万科米辛治疗提供了基础.
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