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了解西斯的药理动力学和毒动力学,以预测和预防损伤

Lauren E Thompson¹, Melanie S Joy²

¹Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences (L.E.T., M.S.J.), University of Colorado Cancer Center (M.S.J.), and Division of Renal Diseases and Hypertension (M.S.J.), University of Colorado Anschutz Medical Campus, Aurora, Colorado laurenethompsonphd@gmail.com.

The Journal of pharmacology and experimental therapeutics

|September 25, 2024

概括

西斯普拉丁化疗经常导致急性损伤 (AKI). 本综述探讨了药理动力学/毒理动力学 (PKTD) 模型和生物标志物,以预测和预防西斯的毒性,改善患者的治疗结果.

科学领域:

腎臟病學 (nephrology) 是一種醫學專業.
药理学药理学是指药理学的学科.
在瘤学瘤学.

背景情况:

基于的化学疗法西斯 (cisplatin) 在大约30%的患者中引起急性损伤 (AKI).
现有的西斯诱导的AKI的药理动力学/毒理动力学 (PKTD) 模型主要利用传统的临床生物标志物.
已知西斯的毒性风险因素,但的药理动力学 (PK) 和损伤生物标志物之间的联系尚不清楚.

研究的目的:

审查临床,小鼠和体外模型中西斯胺诱导的毒性评估.
为了检查可用的人类PK和毒力学 (TD) 数据对西斯.
强调需要改进的PKTD模型,包括敏感的损伤生物标志物和风险因素.

主要方法:

关于西斯的毒性研究的文献综述.
对西斯的药理动力学和毒理动力学的临床和临床前数据的分析.
检查传统和亚临床损伤生物标志物.

主要成果:

发表的PKTD模型用于西斯普拉丁诱导的AKI仅限于传统生物标志物 (例如SCr,BUN,eGFR).
亚临床生物标志物 (例如,KIM-1,NGAL,B2M) 提供了早期和更敏感地检测损伤的潜力.
金PK,TD和损伤生物标志物之间的关系需要进一步阐明.

结论:

更好地了解PK/TD关系,包括风险因素,对于预测和预防西斯诱导的AKI至关重要.
开发结合敏感损伤生物标志物和相关共变量的PKTD模型将有助于预防西斯的毒性.
改善预测和预防策略是必不可少的,因为西斯普拉丁诱导的AKI的发病率很高.

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