Drug synergism: its detection and applications.
By R. Tallarida. Journal of Pharmacology and Experimental Therapeutics, 2001
724 citations recorded by the source corpus.
Two drugs that produce overtly similar effects will sometimes produce exaggerated or diminished effects when used concurrently. A quantitative assessment is necessary to distinguish these cases from simply additive action. This distinction is based on the classic pharmacologic definition of additivity that, briefly stated, means that each constituent contributes to the effect in accord with its own potency. Accordingly, the relative potency of the agents, not necessarily constant at all effect levels, allows a calculation using dose pairs to determine the equivalent of either agent and the effect by using the equivalent in the dose-response relation of the reference compound. The calculation is aided by a popular graph (isobologram) that provides a visual assessment of the interaction but also requires independent statistical analysis. The latter can be accomplished from calculations that use the total dose in a fixed-ratio combination along with the calculated additive total dose for the same effect. Different methods may be used, and each is applicable to experiments in which a single drug is given at two different sites. When departures from additivity are found, whether in "two-drug" or "two-site" experiments, the information is useful in designing new experiments for illuminating mechanisms. Several examples, mainly from analgesic drug studies, illustrate this application. Even when a single drug (or site) is used, its introduction places it in potential contact with a myriad of chemicals already in the system, a fact that underscores the importance of this topic in other areas of biological investigation.
Subfields: Analytical Chemistry, Computational Theory and Mathematics, Spectroscopy
View Paper: https://www.semanticscholar.org/paper/a00aa7e0ee6a9b03dcebe42818a84c159b1acc4d
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Citations in the corpus
- ApJ, in press (1999, positive): “…a specific prediction that follows from the null hypothesis: if the interaction is dose-additive, then a 1:1 combination of IFN-b and IFN-g will reduce log (viral DNA yield) by the average of V(b) and V(g) at all points along a dose–response curve (Tallarida, 2000, 2001; Tallarida et al., 1997).”
- Molecular Systems Biology Peer Review Process File Indi: a Computational Framework for Inferring Drug Interactions and Their Associated Recommendations Transaction Report (neutral): “A different approach is employed for predicting pharmacodynamic interactions, depending primarily on combining single drug in-vitro or in-vivo measurements of pharmacodynamic constants (Tallarida, 2001; Jonker et al, 2005; Li et al, 2007).”
- Analysis of drug combinations: current methodological landscape (2015, background): “It is clear from the paradoxes illustrated in Figure 2 that the interpretation of drug combination effects requires a minimal knowledge of the single dose–effect curves within the range of effect of interest (Berenbaum 1977; Greco et al. 1995; Tallarida 2001; Goldoni and Johansson 2007; Lee and Kong”
- A drug burden index to define the functional burden of medications in older people. (2007, methodology): “33 Thus, a simple linear additive model was used to estimate the total B AC and B S .”