Isobolare

Isobolare, also referred to as an isobole or, in Italian, isobolo, is a concept in pharmacology and toxicology that describes a curve or line representing all combinations of two drugs (or agents) that produce the same specified biological effect, such as 50% of the maximal response (ED50). It is a graphical tool used to analyze interactions between drugs in a two-drug mixture.

The isobole is constructed by plotting the dose of one drug on the x-axis and the dose of the other on the y-axis. For a given effect level, the set of dose pairs (a, b) that achieve that effect forms the isobole. Under a Loewe additivity framework, the additive isobole is defined by a relationship that, in simple terms, can be expressed as a/ED50_A + b/ED50_B = 1 when the drugs have similar mechanisms and dose–response characteristics. In practice, the exact shape may be curved or straight depending on the relative potencies and the shapes of the individual dose–response curves.

Interpretation of the position of experimental combinations relative to the isobole informs about drug interactions: points on the line indicate additivity, points below the line suggest synergy (enhanced effect at lower doses), and points above the line indicate antagonism. Isobolographic analysis is widely used in drug development, oncology, and toxicology to optimize combination therapies and to characterize interaction types.

Limitations include its reliance on accurate dose–response models, the assumption of similar mechanisms, and potential confounding pharmacokinetic factors. The method remains a standard approach alongside related concepts such as Bliss independence and combination index analysis.