| Pharmacokinetic/pharmacodynamic modeling and simulation to determine effective dosage regimens for doripenem. | |
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MedLine Citation:
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PMID: 19904828 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Takayuki Katsube; Yoshitaka Yano; Toshihiro Wajima; Yoshinori Yamano; Mikihisa Takano |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Journal of pharmaceutical sciences Volume: 99 ISSN: 1520-6017 ISO Abbreviation: J Pharm Sci Publication Date: 2010 May |
Date Detail:
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Created Date: 2010-03-16 Completed Date: 2010-06-25 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2985195R Medline TA: J Pharm Sci Country: United States |
Other Details:
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Languages: eng Pagination: 2483-91 Citation Subset: IM |
Affiliation:
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Clinical Research Department, Shionogi & Co., Ltd, Sagisu 5-12-4, Fukushima-ku, Osaka 553-0002, Japan. takayuki.katsube@shionogi.co.jp |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Anti-Bacterial Agents*
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administration & dosage,
pharmacokinetics,
pharmacology Carbapenems* / administration & dosage, pharmacokinetics, pharmacology Computer Simulation Dose-Response Relationship, Drug Drug Administration Schedule Microbial Sensitivity Tests Models, Biological* Monte Carlo Method Pseudomonas aeruginosa / drug effects |
| Chemical | |
Reg. No./Substance:
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0/Anti-Bacterial Agents; 0/Carbapenems; 0/doripenem |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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