کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2485917 | 1114370 | 2010 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Pharmacokinetic/pharmacodynamic modeling and simulation to determine effective dosage regimens for doripenem
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کلمات کلیدی
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
اکتشاف دارویی
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چکیده انگلیسی
The aim of this study was to obtain information on effective dosage regimens of doripenem by a modeling and simulation approach based on pharmacokinetic (PK)/pharmacodynamic (PD) theory. The PK/PD model we have already developed was modified to explain in vitro bactericidal kinetics of doripenem for several Pseudomonas aeruginosa strains. Time-course profiles of bacterial counts in patients infected with P. aeruginosa were simulated for typical clinical dosage regimens in Japan considering the variability of PK and the patients' backgrounds by a Monte Carlo simulation. Moreover, time-course profiles of probability achieving the criterion (log(CFU/mL) < 0) were predicted for the evaluation of antibacterial efficacy by renal function. The in vitro bacterial profiles at various dosage regimens could be well explained by the PK/PD model. The simulations suggested the dependence of antibacterial efficacy on the frequency of administration, indicating time-dependent antibacterial activity. It was also suggested that 500 mg t.i.d. showed significant bacterial reduction in patients for any degree of renal function and any severities in 2 weeks after the start of treatment. Our approach to simulate time-course profiles of bacterial counts should be useful for determining and examining effective dosage regimens, including the treatment period, in drug development. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99: 2483-2491, 2010
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 99, Issue 5, May 2010, Pages 2483-2491
Journal: Journal of Pharmaceutical Sciences - Volume 99, Issue 5, May 2010, Pages 2483-2491
نویسندگان
Takayuki Katsube, Yoshitaka Yano, Toshihiro Wajima, Yoshinori Yamano, Mikihisa Takano,