中国临床药理学杂志2018，Vol.34Issue(9)：1048-1051,4.DOI:10.13699/j.cnki.1001-6821.2018.09.012
抗肿瘤化合物TM208在乳腺癌中抑制雌激素的药代动力学-药效学研究
Pharmacokinetic and pharmacodynamic study of chinfloxacin hydrochloride in Chinese adult healthy subjects
冀希炜 1季双敏 2朱校 3卢炜 4周田彦4
作者信息
- 1. 北京大学第一医院临床药理研究,北京100191
- 2. 国家食品药品监督总局药品审评中心,北京100022
- 3. 奥塔哥大学药学院,新西兰达尼丁
- 4. 北京大学医学部药学院,北京100191
- 折叠
摘要
Abstract
Objective To investigate the profiles of resistance following continuous treatment with TM208 using pharmacokinetics/pharmacodynamic (PK/PD) model,as well as to characterize the estrogen levels in hibition in human breast cancer xenograft mice.Methods MCF-7 xenograftnudemice were given TM208 (150 mg · kg-1 · d-1) or vehicle orally for 18 days.The concentrations of estrogen were measured using the human estrogen ELISA kit.The pharmacokinetics and pharmacodynamics of TM208 were evaluated after administration.A one-compartment model with first order absorption was developed to describe the pharmacokinetics of TM208,and the time course of estrogen degradation was characterized by the indirect response model.Tolerance model was used to describe drug resistance of tumor.Results The simulation results showed that the inhibitory effects of TM208 on estrogen may decrease after continuous administration,and the KTO was 0.68 h-1 Conclusion The established PK/PD model allowed a better understanding of the role of estrogen inhibition in breast cancer treatment with TM208.Simulation based on the estrogen model allowed prediction of the detailed processes of TM208 effects on estrogen.Furthermore,the tolerance model-based modeling and simulation methods provided an option for the description and prediction of estrogen resistance.关键词
乳腺癌/药代动力学/药效学模型/仿真/雌激素/TM208Key words
breast cancer/pharmacokinetic/pharmacodynamic model/simulation/estrogen/TM208分类
医药卫生引用本文复制引用
冀希炜,季双敏,朱校,卢炜,周田彦..抗肿瘤化合物TM208在乳腺癌中抑制雌激素的药代动力学-药效学研究[J].中国临床药理学杂志,2018,34(9):1048-1051,4.
