کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10162401 | 1114328 | 2014 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Pharmacokinetic/Pharmacodynamic Modeling for Concentration-Dependent Bactericidal Activity of a Bicyclolide, Modithromycin
ترجمه فارسی عنوان
مدل سازی فارماکوکینتیک / فارماکودینامیک برای فعالیت ضد باکتری وابسته به غلظت یک بیتی کلولید، ماتری ترومایسین
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کلمات کلیدی
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
اکتشاف دارویی
چکیده انگلیسی
The aim of this study was to develop a pharmacokinetic (PK)/pharmacodynamic (PD) model of a bicyclolide, modithromycin, to explain its concentration-dependent bactericidal activity based on the drug-bacterium interaction model that we developed. We have already reported the applicability of model to the time-dependent activity of β-lactams, and we further applied the model to the concentration-dependent activity in this study. In vitro time-kill data of modithromycin, telithromycin, and clarithromycin against Staphylococcus aureus, Haemophilus influenzae, and treptococcus pneumoniae were used for the modeling. An effect compartment model was incorporated into our original model to explain the time lag between PK and PD profiles. Also, a turnover model for reversible reduction of efficacy was incorporated to explain the regrowth. The developed model well described the time-kill profiles for each drug-bacterium combination. The estimated parameter related to efficacy strongly correlated with minimum inhibitory concentration (MIC), and the simulated bacterial counts at 24 h strongly correlated with both the ratio of the area under the concentration-time curve to MIC (AUC/MIC) and the ratio of the maximum concentration to MIC (Cmax/MIC). These results suggested that the proposed model can be applied to both concentration-dependent and time-dependent bactericidal kinetics, and would be useful for predicting the bactericidal activity of modithromycin. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:1288-1297, 2014
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 103, Issue 4, April 2014, Pages 1288-1297
Journal: Journal of Pharmaceutical Sciences - Volume 103, Issue 4, April 2014, Pages 1288-1297
نویسندگان
Takayuki Katsube, Toshihiro Wajima, Yoshinori Yamano, Yoshitaka Yano,