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使用脏损伤分子-1生物标志物的cisplatin脏毒性的药理动力学/毒理动力学模型
Lauren E Thompson1, Avisek Ghimire1, Xia Wen2,3
1Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, USA.
帕洛诺塞特龙可能会减少西斯普拉丁诱导的损伤. 这项研究开发了一种PKTD模型,显示与palonosetron相比,ondansetron增加了暴露和损伤标志物.
科学领域:
- 药理学 药理学是指药理学的学科.
- 腎臟病學 (nephrology) 是一種醫學專業.
- 在瘤学瘤学.
背景情况:
- 西斯普拉丁化疗经常导致急性损伤 (AKI).
- 了解西斯的药理动力学/毒理动力学 (PKTD) 关系对于减轻AKI至关重要.
- 损伤分子-1 (KIM-1) 是AKI的一个生物标志物.
研究的目的:
- 开发一个人群PKTD模型用于西斯普拉丁诱导的AKI.
- 将血总和尿液KIM-1度纳入模型.
- 为了评估5-HT3抗剂抗emetics对西斯甲状腺毒性的影响.
主要方法:
- 使用Phoenix NLME开发了一个非线性混合效应群体PKTD模型.
- 39名癌症患者的血总和尿液KIM-1度在10天内被测量.
- 通过逐步分析确定了影响PKTD参数的共变量.
主要成果:
- 一个两部分的模型描述了的药理动力学,并扩展到PKTD模型,其中包括尿路KIM-1.
- 之前暴露于西斯,5-HT3A抗药和基线KIM-1影响了PKTD参数.
- 与palonosetron相比,Ondansetron增加了 (163%) 和KIM-1水平 (94-235%) 的暴露.
结论:
- 帕洛诺塞特龙可能是一个首选的5-HT3A抗药,以减少西斯普拉丁诱导的损伤.
- PKTD模型提供了对影响西斯甲毒性因素的见解.
- 有针对性的抗选择可以潜在地减轻化疗相关的器官损伤.
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