在瘤学中精准医学:在肥胖癌症患者群体中使用虚拟临床试验的伊马替尼布剂量
Khairulanwar Burhanuddin1,2, Afzal Mohammed2, Nurul Afiqah Burhanuddin3
1National Pharmaceutical Regulatory Agency, Ministry of Health Malaysia, Petaling Jaya, Malaysia.
肥胖会影响癌症患者的伊马替尼布药物水平. 基于生理学的药物动力学建模和治疗药物监测可以帮助优化肥胖个体的剂量,但有些可能需要替代治疗.
科学领域:
- 药理学 药理学是指药理学的学科.
- 在瘤学瘤学.
- 生物医学工程 生物医学工程
背景情况:
- 肥胖会改变药物的药理动力学,这可能会影响癌症治疗的疗效.
- 伊马替尼布是治疗各种癌症的关键向疗法,但在肥胖患者中,其剂量可能需要调整.
研究的目的:
- 通过PBPK建模,研究肥胖对伊马蒂尼布药理学的影响.
- 评估TDM引导的剂量调整,以优化肥胖癌症患者的伊马蒂尼布最低度.
主要方法:
- 使用了基于生理学的药理动力学 (PBPK) 建模和虚拟临床试验.
- 使用临床数据验证了PBPK模型,这些临床数据来自瘦身,超重和肥胖癌症患者队列.
- 模拟评估了生理差异及其对伊马替尼布暴露的影响.
主要成果:
- 肥胖患者的最大度和AUC显着较低,Cmin水平始终较低.
- 较高比例的肥胖个体具有亚治疗性意马替尼 Cmin (< 750 ng/mL).
- 以TDM为指导的剂量调整改善了Cmin,但对于450-750 ng/mL之间的水平,需要高1.5-2.0倍的剂量.
结论:
- 肥胖症显著影响伊马替尼的药理动力学,需要个性化剂量策略.
- 在肥胖癌症患者中,PBPK建模和TDM是优化伊马替尼治疗的重要工具.
- 对于Cmin非常低 (<450 ng/mL) 的患者,进一步的剂量升级可能是有限的,这表明需要替代疗法.
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