A general formulation of the concept of independent action for the combined effects of agents.
Analysis schemes for the classification of synergism and antagonism for mixed agents operate on the discrepancies between observed and calculated results. As such they cannot be confirmed by experiments and therefore have to be tested in terms of mathematical and logical self-consistency. The concept of independent action is close to the literal meaning of the term "non-interaction". Since this concept does not depend on the mechanisms of actions nor on the type of effect scale used, it is suitable as one of the basic criterion for the definition of synergism and antagonism. A general mathematical framework of independent action is presented in this paper based on the concept of "relative effect" as used in the literature. The different equations for independent action currently used in various areas are shown to be manifestations of a general formula under different sets of boundary conditions, which are the natural limiting values of the effects of the corresponding system observed at low and at high doses of the agents. The framework can be generalized to the combined action of n-agents as well as to the interaction of an agent with itself. In addition, the differential form of the formula for independent action is derived. This framework of systematic definitions and derived equations enable a more in-depth study of the implications of the concept of independent action and its relation to other concepts of non-interaction.
Lam
G K
GK
Batho Biomedical Facility, TRIUMF, University of British Columbia, Vancouver, Canada.
D000818:Animals; D004336:Drug Antagonism; D004347:Drug Interactions; D004357:Drug Synergism; D006801:Humans; D008433:Mathematics; D008954:Models, Biological