在小儿固体器官移植受体中使用塔克罗利的群体药动力学模型:系统性审查
Kanyaporn Khamlek1, Virunya Komenkul1, Tatta Sriboonruang1
1Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand.
British journal of clinical pharmacology
|September 15, 2023
概括
本综述总结了儿科塔克罗利群体的药动力学模型,确定了体重,CYP3A5基因型和移植后几天作为影响移植患者药物清除的关键因素.
科学领域:
- 药理学 药理学是指药理学的学科.
- 临床药房 临床药房
- 儿科移植医学 儿科移植医学
背景情况:
- 塔克罗利马斯是儿科固体器官移植中至关重要的免疫抑制剂.
- 了解塔克罗利斯的药理动力学对于优化治疗结果和尽量减少儿童的毒性至关重要.
- 现有的药理动力学模型需要定期更新,以反映当前的临床实践和患者群体.
研究的目的:
- 编制和分析目前儿童移植受体中塔克罗利斯的人口药动力学 (PopPK) 模型.
- 确定导致该患者群体中塔克罗利斯药理动学的变化的主要因素.
- 评估现有PopPK研究中使用的建模方法和验证方法.
主要方法:
- 在主要的科学数据库 (Web of Science,PubMed,Scopus等) 中进行了系统的文献搜索. 在2023年3月之前.
- 包括专注于儿科实体器官移植患者的研究,使用非线性混合效应建模 (NLME) 来测量塔克罗利斯的药理动力学.
- 数据提取侧重于模型结构,共变效应和报告的药物动力学参数.
主要成果:
- 审查了21项研究,主要涉及肝脏 (62%) 和脏 (33%) 移植接受者.
- 一个隔间模型是最常见的;体重显著预测分布体积 (Vd/F).
- 塔克罗利斯清除受体重,移植后几天,CYP3A5基因型和血红素的影响,具有显著的个体间变异性 (13.5110.0%).
结论:
- 本综述提供了对影响儿科患者塔克罗利斯药理动学的因素的见解,有助于临床预测药物清除.
- 临床医生可以利用体重,CYP3A5基因型,移植后几天或血红素值来估计塔克罗利斯清除值.
- 需要进一步的研究来探索药理遗传学-药理动力学关系以及非线性动力学在儿科群体中的适用性.
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