A mathematical model for cisplatin cellular pharmacodynamics
A mathematical model for cisplatin cellular pharmacodynamics
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DOI：
10.1016/s1476-5586(03)80008-8
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发表时间：
2003-03-01
期刊：
影响因子：
4.8
通讯作者：
Secomb, TW
中科院分区：
文献类型：
--
作者：
El-Kareh, AW;Secomb, TW
顺铂的细胞药效学的一个简单的理论模型。该模型，它考虑到顺铂的细胞摄取的动力学和药物的细胞内结合，可用于预测依赖的生存（相对于控制）的时间过程中的细胞外暴露。细胞药代动力学参数来源于人卵巢癌和头颈癌细胞系的摄取数据。假设相对于对照的存活率取决于DNA结合的细胞内铂的峰浓度。模型预测同意与顺铂细胞毒性的三种不同的癌细胞系，在广泛的曝光时间的公布数据。与以前发表的抗癌药物药效学数学模型相比，本模型提供了更好的拟合实验数据集，包括长暴露时间（类似于100小时）。该模型提供了一个可能的解释的事实，即细胞杀伤相关的细胞外浓度-时间曲线下面积在某些数据集，但不是在其他。该模型可能是有用的优化交付时间表和顺铂治疗癌症的剂量。
A simple theoretical model for the cellular pharmacodynamics of cisplatin is presented. The model, which takes into account the kinetics of cisplatin uptake by cells and the intracellular binding of the drug, can be used to predict the dependence of survival (relative to controls) on the time course of extracellular exposure. Cellular pharmacokinetic parameters are derived from uptake data for human ovarian and head and neck cancer cell lines. Survival relative to controls is assumed to depend on the peak concentration of DNA-bound intracellular platinum. Model predictions agree well with published data on cisplatin cytotoxicity for three different cancer cell lines, over a wide range of exposure times. In comparison with previously published mathematical models for anticancer drug pharmacodynamics, the present model provides a better fit to experimental data sets including long exposure times (similar to100 hours). The model provides a possible explanation for the fact that cell kill correlates well with area under the extracellular concentration-time curve in some data sets, but not in others. The model may be useful for optimizing delivery schedules and for the dosing of cisplatin for cancer therapy.