Loewe additivity
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In toxicodynamics and pharmacodynamics, Loewe additivity (or dose additivity) is one of several common reference models used for measuring the effects of drug combinations.[1][2][3]
Definition
Let and be doses of compounds 1 and 2 producing in combination an effect . We denote by and the doses of compounds 1 and 2 required to produce effect alone (assuming this conditions uniquely define them, i.e. that the individual dose-response functions are bijective). quantifies the potency of compound 1 relatively to that of compound 2.
can be interpreted as the dose of compound 2 converted into the corresponding dose of compound 1 after accounting for difference in potency.
Loewe additivity is defined as the situation where or .
Geometrically, Loewe additivity is the situation where isoboles are segments joining the points and in the domain .
If we denote by , and the dose-response functions of compound 1, compound 2 and of the mixture respectively, then dose additivity holds when
Testing
The Loewe additivity equation provides a prediction of the dose combination eliciting a given effect. Departure from Loewe additivity can be assessed informally by comparing this prediction to observations. This approach is known in toxicology as the model deviation ratio (MDR).[4]
This approach can be rooted in a more formal statistical method with the derivation of approximate
References