Unification of Pharmacodynamic Models

A very general scheme for relating effects to concentration, of which both the effect-compartment and the indirect-effect models are special cases, was outlined by Sheiner and Verotta [452], The models presented in the study can be considered to be a special case of that unified scheme. As judiciously presented by these authors, both direct-response and indirect-response models are composed of one nonlinear static submodel and one dynamic submodel, but the placement of the submodels in the global model differs  

All these models introducing the prereceptor and postreceptor events have an interesting appeal with respect to physiologically implied mechanisms. Sheiner and Verotta [452] pointed out the importance of knowing where the rate-limiting step is located in a series of events from pre- to postreceptor drug interactions. 

The fundamental assumption and equations governing the effect-concentration relationship for each one of the models considered are listed in Table 10.1. The presence or not of an hysteresis loop in the effect-plasma concentration plot of each model is also quoted in Table 10.1. At present, the methodology for performing efficient pharmacokinetic-dynamic modeling is well established [405,456,457], 

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