Effect-compartment model

Therefore, we can conclude that hystersis can be of PK origin or of PD origin in the case of latter origin it is desired to sample the site of action if possible, otherwise resort to hypothetical effect-compartment modeling (see below). Running numerous steady-state experiments does not prove very useful or practical in such situations. 

There may be several reasons for this pattern to be observed. One obvious reason is distribution, i.e. the drug needs time to reach its site of action, and the time lag between the measured drug concentration in plasma and the drug effect is due to distributional delay. In order to describe such a plasma concentration-effect relationship, a PK-PD model that allows for drug distribution to the site of action, e.g. the effect compartment model may be used. 

The effect compartment model assumes that the pharmacological effect is produced in a hypothetical, exceedingly small compartment, added to the... 

The effect-compartment model relaxes the assumption H3 and it stems from the assumption of prereceptor nonequilibrium between drug concentration in the blood or plasma c (t) and the receptor site y (t). According to this model, an additional compartment is considered, the effect (or biophase) compartment, and... 

The standard effect-compartment model, usually characterized as an atypical indirect-link model, also constitutes an example of what we will call a direct-response model in contrast to the indirect-response models. Globally, the standard direct-response models are models in which c(t) affects all dynamic processes only linearly. 

Holford NHG. Physiological alternatives to the effect compartment model. In D Argenio DZ, editor. Advanced methods of pharmacokinetic and pharmacodynamic systems analysis. New York Plenum Press 1991. p.55-68. 

For other models, such as indirect-response [105] and effect-compartment models [106], it is necessary to model more complex effect-time relationships. 

When the hypothetical effect-compartment model (40) is applied to such data, the model is usually quite good when fitted to the drug response at individual doses however, the model parameters are often dose-dependent and the model does a poor job when fitted to data from several doses simultaneously (6,28). The utility of the hypothetical effect-compartment model in predicting responses at other doses, therefore, is limited. 

To inhibit cholinesterase within the red blood cell (RBC), zifrosilone must first cross the RBC membrane. Hence, there may be a delay in effect. The next model examined was an effect compartment model, which models the effect of a drug based on the drug concentration in a hypothetical effect compartment. In this instance an effect compartment, denoted Ce, with the same first-order rate constant for input and output (ke) was modeled with the observed drug effect dependent on the effect compartment concentration through an Emax model... 

---