Pharmacokinetic and pharmacodynamic study of chinfloxacin hydrochloride in Chinese adult healthy subjects
10.13699/j.cnki.1001-6821.2018.09.012
- VernacularTitle: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
- Author:
Xi-Wei JI
1
;
Shuang-Min JI
;
Xiao ZHU
;
Wei LU
;
Tian-Yan ZHOU
Author Information
1. 北京大学第一医院临床药理研究
- Keywords:
breast cancer;
pharmacokinetic/pharmacodynamic model;
simulation;
estrogen;
TM208
- From:
The Chinese Journal of Clinical Pharmacology
2018;34(9):1048-1051
- CountryChina
- Language:Chinese
-
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.
