| Autor: |
Brun, Y. F., Segal, B. H., Dennis, C. G., Youn, R. C., White, D. B., Greco, W. R. |
| Předmět: |
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| Zdroj: |
Clinical Pharmacology & Therapeutics; Feb2006, Vol. 79 Issue 2, pP28-P28, 1p |
| Abstrakt: |
Background: Various approaches to the assessment of synergy, additivity and antagonism among drugs have been developed, including graphical isobologram and statistical response surface methods. Response surface methods allow one to model all of the information present in full multiple-agent concentration-effect data sets, and to quantify local regions of synergy, additivity, and antagonism.Methods: In vitro, Aspergillus fumigatus was exposed in randomized wells of 96-well plates to combinations of Amphotericin B, Nikkomycin Z and Micafungin. It included full concentration-effect curves for each agent alone; 3 fixed-ratio each of the 3 binary mixtures; and 11 fixed-ratio ternary mixtures. Each curve had 11 different concentrations (plus control), all performed in quintuplicate. After 24-h exposure, fungal growth was assessed with an XTT assay.Results: We modeled each fixed-ratio combination alone using the 4 parameter Hill concentration-effect model. Then, we modeled each parameter versus the proportion of each agent using constrained polynomials. Finally, we modeled the three-agent response surface overall. The overall 4-dimensional response surface is complex, but can be explained in detail. Zones of synergy, additivity and antagonism are mapped on the surface.Conclusions: Applying this response-surface method to a huge dataset for a three-antifungal agent combination is novel and has the potential to revolutionize the field of antifungal pharmacology.Clinical Pharmacology & Therapeutics (2005) 79, P28–P28; doi: 10.1016/j.clpt.2005.12.102 [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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