Intracellular Pharmacokinetics of Activated Drugs in a Prodrug-Enzyme-Ultrasound System: Evaluations on ZD2767P+CPG2+US
作者全名："Yu, Tinghe; Li, Xinya; Yu, Tianran; Chen, Mengjie; Sun, Yong; Ran, Rui"
作者地址："[Yu, Tinghe; Li, Xinya; Chen, Mengjie; Ran, Rui] Chongqing Med Univ, Affiliated Hosp 2, Lab Obstet & Gynecol, Chongqing 400010, Peoples R China; [Yu, Tianran] Yangjiaping High Sch, Chongqing 400039, Peoples R China; [Sun, Yong] Sichuan Mianyang 404 Hosp, Dept Emergency Med, Mianyang 621000, Peoples R China"
通信作者："Yu, TH (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Lab Obstet & Gynecol, Chongqing 400010, Peoples R China."
来源：ACS MEDICINAL CHEMISTRY LETTERS
ESI学科分类：CHEMISTRY
WOS号：WOS:001197289400001
JCR分区：Q2
影响因子：4.2
年份：2024
卷号：
期号：
开始页：
结束页：
文献类型：Article; Early Access
关键词：Intracellular pharmacokinetics; Prodrug-enzyme-ultrasoundtherapy; ZD2767D; Experimental design; Pharmacokinetics model; Therapeutic implications
摘要："Intracellular pharmacokinetics (PK) of activated drugs is a window to understanding the pharmacodynamics of prodrug-enzyme-ultrasound therapy. Herein PK of ZD2767D (i.e., activated drug) in the ZD2767P+CPG2+US system on A549, A549/DDP, SKOV3, and SKOV3/DDP cells were evaluated (A549/DDP and SKOV3/DDP were cisplatin-resistant sublines). The noncompartment model under extravascular input mode was deemed appropriate for evaluating drug level vs time curves; C-max, AUC(last), MRTlast, V-z, and Cl can reflect the PK feature, but t(1/2), AUC(inf), and MRTinf were irrational; higher accumulation and slower elimination characterized the PK mechanism of ZD2767P+CPG2+US; enhanced permeability and retention effect can be assessed with C-max, AUC(last), MRTlast, and t(last); ultrasound equivalently modulated C-max and AUC(last) in sensitive and resistant cells. The experimental design and dose proportionality were discussed."
基金机构：Eyas Project from Chongqing Municipal Educational Commission
基金资助正文：Tianran Yu was funded with the Eyas Project from Chongqing Municipal Educational Commission.
