کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
10161966 1114307 2015 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Semi-Mechanism-Based Pharmacokinetic/Pharmacodynamic Model for the Combination Use of Dexamethasone and Gemcitabine in Breast Cancer
ترجمه فارسی عنوان
مدل فارماکوکینتیک / فارماکودینامیک مبتنی بر نیمه مکانیسم برای استفاده ترکیبی از دگزامتازون و گمسیتابین در سرطان پستان
کلمات کلیدی
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی اکتشاف دارویی
چکیده انگلیسی
Our study aimed at the investigation of in vivo anticancer effect of the combination use of dexamethasone (DEX) and gemcitabine (GM) as well as the development of pharmacokinetic/pharmacodynamic (PK/PD) models in MCF-7 xenograft model. Further, simulations were conducted to optimize doses and administration schedules. The inhibitory effect of different doses and administration schedules were investigated in MCF-7 xenograft model. Semi-mechanism-based PK/PD models were established based on the preclinical data to characterize the relationship between plasma concentration and the time course of the drug response quantitatively. The PK/PD models were further applied to predict and optimize doses and administration schedules, which would lead to tumor stasis by the end of the treatment. Synergistic effect was observed in the PD study in vivo and further confirmed by the estimated combination index ψ obtained from PK/PD models. The optimum dose regimen was selected as DEX 2 mg/kg, qd and GM 10 mg/kg, q2d based on the simulation results. In summary, the PD interaction between DEX and GM was demonstrated as synergism by both experimental results and modeling approach. Dosage regimens were optimized as predicted by modeling and simulations, which would provide reference for preclinical study and translational research as well.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 104, Issue 12, December 2015, Pages 4399-4408
نویسندگان
, , , , , , , , , ,