药物遗传检测或治疗药物监测:一个定量框架
Maddalena Centanni1, Niels Reijnhout1, Abel Thijs2
1Department of Pharmacy, Uppsala University, Box 580, 751 23, Uppsala, Sweden.
Clinical pharmacokinetics
|June 6, 2024
概括
药物遗传学分析优于治疗药物监测 (TDM) 在特定情况下估计药物暴露,特别是当个体间变异性较低而其他变异性较高时. 对于具有较低残留和间偶变性的药物,TDM仍然是最好的.
科学领域:
- 药物动力学和药物基因组学
- 临床药理学 临床药理学
- 药物的新陈代谢和处置
背景情况:
- 药物暴露的个体间变异性 (IIV) 需要个性化剂量策略.
- 药物遗传学分析和治疗药物监测 (TDM) 是管理这种变化的关键方法.
- 估计药物暴露的最佳策略因药物和变化源而异.
研究的目的:
- 量化评估何时药物遗传学分析在估计药物暴露时优于TDM.
- 调查IIV,间场变性 (IOV) 和残余不明原因变性 (RUV) 对每个方法的性能的影响.
- 为药物剂量个性化提供支持临床决策的数据.
主要方法:
- 从药物文学中选择的药物动力学模型,包括药物遗传学和TDM考虑.
- 在IIV,IOV和RUV的不同水平下,模拟的药物暴露 (深度度或AUC)
- 在六个药物病例中比较了药物遗传学概况与TDM的预测性能.
主要成果:
- 药物遗传学分析对TDM的优越性因药物而异:5-甲 (100%),温克里斯 (49.6%),RISPERIDONE (48.1%),埃法维伦兹 (49.2%),塔莫西芬 (12.7%) 和塔克罗利斯 (11.0%).
- 当无法解释的IIV高,而RUV/IOV低时,TDM优越.
- 当无法解释的IIV较低,IOV/RUV较高时,药物遗传学分析是首选的.
结论:
- 对于具有较低RUV和IOV的药物 (例如,他莫西芬,塔克罗利斯),TDM提供了最佳的暴露估计.
- 对于低无法解释的IIV和高RUV的药物 (例如,efavirenz,5-FU),对于大多数患者来说,药物遗传学概况更准确.
- 诸如基因型患病率,对PK的遗传影响以及TDM估计AUC的能力等因素影响了策略的选择.
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