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Comment
. 2013 Nov;154(11):3974-7.
doi: 10.1210/en.2013-1420. Epub 2013 Sep 3.

Synergy: a concept in search of a definition

Hans-Rudolf Berthoud  1
Affiliations
Comment

Synergy: a concept in search of a definition

Hans-Rudolf Berthoud. Endocrinology. 2013 Nov.
No abstract available

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Figures

Figure 1.
Figure 1.
Response additivity can produce erroneous predictions for drugs or biological agents with curvilinear dose-effect relationships. In the example shown, the effect of dose 2 is 1, so that according to the principle of sham combinations, doubling the dose from 2 to 4 would be predicted to yield a response of 2 × 1 = 2. In fact, due to the concave-up shape of the dose-effect curve in that range, the observed effect of dose 4 is 5.3, or more than twice as large as predicted. Thus, nondiscerning use of response additivity can erroneously lead to the conclusion that low doses of this drug synergize potently with themselves. Because almost all dose-effect curves are accelerating in the region of threshold doses, the problem is particularly pertinent to response addition of 2 subthreshold doses. Adapted from Geary (4) with permission.
Figure 2.
Figure 2.
Graphic illustration of the dose-equivalence principle yielding indeterminate Loewe-additive solutions. A, Dose 1 of A is equivalent to dose 3.2 of B (dashed lines), and dose 1 of B is equivalent to dose 0.3 of A (full lines), as explained in the text. B, Note that different additive predictions are generated for combination of doses 1 of A plus 1 of B when the A-equivalent dose of B is used (full lines; 1.3 units of A yields effect of 5.2) than when the B-equivalent dose of A is used (dashed lines; 4.2 units of B yields effect of 6.3) is used. In many cases the disparity is much greater. Adapted from Geary (4) with permission.
See this image and copyright information in PMC

Comment on

  • Understanding synergy.
    Geary N. Geary N. Am J Physiol Endocrinol Metab. 2013 Feb 1;304(3):E237-53. doi: 10.1152/ajpendo.00308.2012. Epub 2012 Dec 4. Am J Physiol Endocrinol Metab. 2013. PMID: 23211518 Review.

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