The interaction index: a measure of drug synergism

TLDR

The interaction index (γ) quantifies how drug combinations enhance or reduce effects, serving as a quantitative marker for potency changes, and in some cases relative potencies remain constant across effect levels. The study demonstrates that when relative potencies are constant, the interaction index can be measured using either isobolar or an alternate method. The authors model dose–effect data with regression to generate linear log‑dose plots, apply isobolar analysis, and use an alternate method when relative potencies are constant, with statistical analysis evaluating precision. The calculations show that both methods produce identical γ values with comparable precision.

Abstract

Two drugs used in combination may produce enhanced or reduced effects. The degree of enhancement or reduction is measured from the interaction index (γ), a quantity that indicates the changed potency of the combination. The index is therefore a quantitative marker for the drug combination and effect metric used. Methodology for measuring the interaction index utilizes the combination and individual drug dose–effect data suitably modeled by regression techniques that most often produce linear plots of effect on log dose from which isobolar analysis is employed. The isobologram provides a simple and convenient graphical assessment of the interaction index but an independent statistical analysis is needed to assess its precision. In some cases, the relative potency of the constituent drugs is the same at all effect levels. When this is so, it is shown that the interaction index can be measured by either an isobolar or an alternate method that is illustrated here. These calculations demonstrate that these different methods of analysis yield the same value of γ, and do so with comparable precision.