Pharmacodynamic Models: Direct Effect Model and Indirect Response Model

Pharmacodynamic models are broadly categorized as direct effect or indirect response models.

Direct effect models link drug concentration to response for drugs rapidly reaching their site of action.

The response may be proportional to concentration in a linear model, or follow an E_max model.

For example, argatroban's plasma concentrations directly relate to its anticoagulant response, which follows an E_max model.

Indirect response models describe how a drug influences the production or elimination of endogenous compounds.

For instance, models I and II describe inhibitory effects on response production and degradation, with I_max capped between 0 and 1. In contrast, models III and IV describe stimulatory effects, with the maximum stimulation value always greater than 0.

These models often display a delayed peak response, gradual response changes, initial rates independent of dose, and a prolonged time to maximum effect at higher doses.

They support dose selection and help assess early drug candidates during development. One example is modeling mizolastine's antihistaminic effect on flare area over time at varying doses.