Evaluation of the type of overadditive drug interaction under various experimental conditions: differentiation of sequential from functional synergism in dose response studies.
Gregory Poch, K Schmidt, P. Dittrich · PubMed · 1983
In the assessment of the pharmacodynamic action and interaction of drugs, frequently the influence of one drug is studied in the presence of a synergistic drug, resulting either in an additive or an overadditive response. The latter may be due to independent (functional synergistic) or interdependent (sequential synergistic) interaction. From dose response experiments in vitro with prototypes of synergistic drugs A and B acting in sequence, it can be deduced how under different experimental situations, i.e. known or unknown, possible maximum response, sequential synergism can be ascertained. The procedure described rests on the evaluation of net effects in addition to total effects of drugs. The net effects of A + B, i.e. of A in the presence of B, match with those of A in the absence of B in case of functional synergism. They markedly exceed it in the cases of sequentially interacting drugs, as shown. The latter can therefore be regarded as examples of sequential synergism and illustrate the assessment of this type of overadditive synergism under different experimental situations.