simple case of an interaction between two drugs,
the three variables are the dose of drug A, the dose
of drug B and size of effect; the last of these being
shown by the contours.
Additivityis where two drugs have the same
effect, and neither potentiates or antagonizes the
other. The isobologram has contours that are par-
allel line segments (see Figure 20.1). If the adverse
effects are different then this tactic can minimize
clinical hazard without sacrificing efficacy. Anti-
biotic combinations frequently are additive.
Antagonismis an interaction where one or other
drug reduces the activity of the other. The contours
of the isobologram are convex away from the ori-
gin of the plot (Figure 20.2). Several examples of
antagonistic interactions are discussed below in
connexion of the locus where such interactions
take place.
Synergy or Potentiationis where the combina-
tion of two drugs has an effect that is greater than
simply additive. The contours of the isobologram
are concave toward the origin of the plot
(Figure 20.3). In most cases, an effect with this
1 3 5 7 9
Dose of drug ADose of drug BE2E6E101 3 5 7 94A + 4B has
same effect (E8)
as 8A or 8B
aloneFigure 20.1 Isobologram illustrating simple additivity. The lines connect equal amounts of drug effect (E), with each
having the general equation ayþbx¼kEc, where a, b and k are constants, andcis the percentage of maximal effect on
the dose–response curve (in this case a¼b¼k¼1)
Dose of drug ADose of drug BE91357913579E6E3Figure 20.2 A classical isobologram illustrating
antagonism. Using the same notation as in Figure
20.1. The broken lines show how a combination of four
units of drug A plus four units of drug B has an effect
that is much less than E8 (as would be the case if the
interaction was additive). The formulae for the contours
are ayþbx<kEc256 CH20 DRUG INTERACTIONS