Characterization of four basic models of indirect pharmacodynamic responses

Four basic models of indirect pharmacodynamic responses were characterized in terms of changing dose, I-max or S-max, and IC50 or SC50 to examine the effects of these fundamental drug properties on response profiles. Standard pharmacokinetic parameters were used for generating plasma concentration, and response-time profiles using computer simulations. Comparisons to theoretical expectations were made. In all four models, the maximum response (R-max) (inhibition or stimulation) and the time of its occurrence (T-Rmax) were dependent on the model, dose, I-max or S-max, and IC50 or SC50 values. An increase in dose or a decrease in IC50 or SC50 by the same factor produced, as theoretically expected identical and superimposable pharmacodynamic response patterns in each of the models. Some parameters (T-Rmax, ABEC) were nearly proportional to log dose, while others (R-max, C-Rmax) were nonlinear. Assessment of expected response signature patterns as demonstrated in this report may be helpful in experimental designs and in assigning appropriate models to pharmacodynamic data.