IMR Press / FBS / Volume 2 / Issue 2 / DOI: 10.2741/S80

Frontiers in Bioscience-Scholar (FBS) is published by IMR Press from Volume 13 Issue 1 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on as a courtesy and upon agreement with Frontiers in Bioscience.

A review of synergy concepts of nonlinear blending and dose-reduction profiles
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1 Drug Development Sciences Department, Research Statistics Unit (UP-4315), GlaxoSmithKline Pharmaceuticals, Rand D, 1250 So Collegeville Road, Collegeville, Pennsylvania 19426, USA

*Author to whom correspondence should be addressed.

Academic Editor: William R. Greco

Front. Biosci. (Schol Ed) 2010, 2(2), 483–503;
Published: 1 January 2010

This article presents a case-study review of synergy concepts of nonlinear blending and dose-reduction profiles. "Strong nonlinear blending" is a novel concept that provides a flexible paradigm for the assessment of combination drug synergy that is applicable to any shaped combination-drug dose-response surface; issues of varying relative potency, partial inhibitors, potentiation, or coalism pose no problems at all. Dose-reduction profiles are overlay plots created to show how much each drug can be reduced in amount and yet achieve the same efficacy as larger amounts of each drug used individually. This review applies these synergy concepts to two data sets from a previously published experiment. The previous publication had claimed a high degree of Loewe synergy for one of the data sets. However, a more penetrating analysis shows that with regard to strong nonlinear blending there is no reason to blend (for purposes of response enhancement) the two compounds studied. However, the dose-reduction profile plots show how Loewe synergy is present and provide further insight to the interaction of the two compounds (on the dose-concentration scale).

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