| Development of an integrated semi-automated system for in vitro pharmacodynamic modelling. | |
| | |
MedLine Citation:
|
PMID: 18647747 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
OBJECTIVES: The aim of this study was to develop an integrated system for in vitro pharmacodynamic modelling of antimicrobials with greater flexibility, easier control and better accuracy than existing in vitro models. METHODS: Custom-made bottle caps, fittings, valve controllers and a modified bench-top shaking incubator were used. A temperature-controlled automated sample collector was built. Computer software was developed to manage experiments and to control the entire system including solenoid pinch valves, peristaltic pumps and the sample collector. The system was validated by pharmacokinetic simulations of linezolid 600 mg infusion. The antibacterial effect of linezolid against multiple Staphylococcus aureus strains was also studied in this system. RESULTS: An integrated semi-automated bench-top system was built and validated. The temperature-controlled automated sample collector allowed unattended collection and temporary storage of samples. The system software reduced the labour necessary for many tasks and also improved the timing accuracy for performing simultaneous actions in multiple parallel experiments. The system was able to simulate human pharmacokinetics of linezolid 600 mg intravenous infusion accurately. A pharmacodynamic study of linezolid against multiple S. aureus strains with a range of MICs showed that the required 24 h free drug AUC/MIC ratio was approximately 30 in order to keep the organism counts at the same level as their initial inoculum and was about > or = 68 in order to achieve > 2 log(10) cfu/mL reduction in the in vitro model. CONCLUSIONS: The integrated semi-automated bench-top system provided the ability to overcome many of the drawbacks of existing in vitro models. It can be used for various simple or complicated pharmacokinetic/pharmacodynamic studies efficiently and conveniently. |
| | |
Authors:
|
Liangsu Wang; Michael K Wismer; Fred Racine; Donald Conway; Robert A Giacobbe; Olga Berejnaia; Gary S Kath |
Related Documents
:
|
19167597 - Models for the prediction of mycophenolic acid area under the curve using a limited-sam... 18559487 - Estimation of human drug clearance using multiexponential techniques. 1302767 - Evaluation of bayesian estimation in comparison to nonmem for population pharmacokineti... 23194537 - A new qsar model, for angiotensin i-converting enzyme inhibitory oligopeptides. 20216657 - Relationship between two analytic inversion formulae for multispectral extinction data. 17121627 - The role of procalcitonin in a decision tree for prediction of bloodstream infection in... |
Publication Detail:
|
Type: In Vitro; Journal Article; Research Support, Non-U.S. Gov't Date: 2008-07-21 |
Journal Detail:
|
Title: The Journal of antimicrobial chemotherapy Volume: 62 ISSN: 1460-2091 ISO Abbreviation: J. Antimicrob. Chemother. Publication Date: 2008 Nov |
Date Detail:
|
Created Date: 2008-10-13 Completed Date: 2008-12-05 Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 7513617 Medline TA: J Antimicrob Chemother Country: England |
Other Details:
|
Languages: eng Pagination: 1070-7 Citation Subset: IM |
Affiliation:
|
Department of Infectious Disease Research, Merck Research Laboratories, 126 E. Lincoln Avenue, Rahway, NJ 07065, USA. liangsu_wang@merck.com |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Acetamides
/
pharmacokinetics,
pharmacology Anti-Bacterial Agents / pharmacokinetics*, pharmacology* Automation* Colony Count, Microbial Humans Microbial Sensitivity Tests Microbial Viability Oxazolidinones / pharmacokinetics, pharmacology Staphylococcus aureus / drug effects* Time Factors |
| Chemical | |
Reg. No./Substance:
|
0/Acetamides; 0/Anti-Bacterial Agents; 0/Oxazolidinones; 165800-03-3/linezolid |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Cefuroxime non-susceptibility in multidrug-resistant Klebsiella pneumoniae overexpressing ramA and a...
Next Document: Light-induced hydrogen bonding pattern and driving force of electron transfer in AppA BLUF domain ph...