PMID: 9416783Jan 1, 1997Paper

Efficient designs for studying synergistic drug combinations

Life Sciences
Ronald J TallaridaR B Raffa

Abstract

Distinguishing between pharmacologically additive and synergistic drug combinations requires experimental designs and statistical analyses that often require appreciable numbers of animals and much experimenter time. The current study employed a design in which individual dose-effect data from each drug were translated into theoretically additive total dose combinations, in a fixed drug proportion, in order to produce a composite additive dose-effect relation that could be compared with that of an actual mixture having the same proportion. Results from this approach, using a combination of intrathecal doses of morphine and clonidine, were virtually identical to those using isobolographic analysis of the same data set. Both analyses showed significant synergism for this combination and, in each method, it was not necessary to constrain the drug regression lines to parallelism. In contrast to the isobole approach, the use of the composite additive dose-effect relation also allows observation of the interaction over a range of effects while reducing the size of the data sets needed.

Associated Clinical Trials

References

Feb 1, 1992·Journal of Surgical Oncology·D Y Hou, Y Maruyama
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Citations

Apr 11, 2006·Naunyn-Schmiedeberg's Archives of Pharmacology·Jarogniew J LuszczkiStanislaw J Czuczwar
Jul 23, 2003·Pharmacology, Biochemistry, and Behavior·Jarogniew ŁuszczkiStanisław J Czuczwar
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