Criteria for Analyzing Interactions between Biologically Active Agents

TLDR: The effect–summation criterion may be used when the effects of all the agents in a combination are directly proportional to dose, and the key to any criterion for examining interactions between different agents lies in the definition of zero interaction.

Abstract: Publisher Summary The existence of any substantial interaction between different agents that are used clinically or to which man is exposed environmentally is potentially of great importance. One agent may affect another's absorption, metabolism, or excretion. It may alter tissue sensitivity to another agent, and may react with it physically or chemically. A variety of different criteria have been devised for deciding whether the agents in a combination interact pharmacologically. The purpose of this chapter is to examine these criteria critically for the progress in this field. To summarize, the effect–summation criterion may be used when the effects of all the agents in a combination are directly proportional to dose. The key to any criterion for examining interactions between different agents lies in the definition of zero interaction. The interactions that can be analyzed by constructing isoboles or calculating interaction indices are not restricted to cases in which all agents in a combination produce the effect under consideration. The therapeutic significance of interactions between agents requires careful consideration.