doseadditivity

Dose additivity is a pharmacological concept describing how the effect of two or more agents with similar mechanisms can be predicted from their doses. In a dose-additive interaction, the combination behaves as if the agents were diluted relative to each other, such that the total effect at a given level can be obtained by summing doses on an equivalent potency scale.

A formal approach to dose additivity is Loewe additivity. For a fixed effect level, let D1 and D2 be the doses of two drugs that produce that effect individually. A combination with doses d1 and d2 is considered additive when d1/D1 + d2/D2 = 1. This relationship underpins the construction of isobolograms, graphs that plot the dose pairs producing the same effect. The line joining (D1, 0) and (0, D2) represents the additive interaction; points on the line indicate additivity, points below the line suggest synergy (the effect is achieved with smaller total doses), and points above the line indicate antagonism (the effect requires larger total doses).

Applications of dose additivity include the assessment of drug combinations in therapy and the evaluation of chemical mixtures in toxicology and risk assessment. Limitations arise when agents have dissimilar mechanisms of action, different dose–response shapes, or non-constant potency; in such cases, the additivity assumption may not hold, and other models of interaction, such as response additivity or independent-action frameworks, may be more appropriate.