WNL Classic Model calculations

Indirect Response models

When the pharmacologic response takes time to develop and the observed response is not directly related to plasma concentrations of the drug a link model can be applied to relate the pharmacokinet­ics of the drug to its pharmacodynamics. Phoenix contains a group of indirect pharmacodynamic response (IPR) models proposed by Jusko (1990) and Dayneka, Garg, and Jusko (1993). The indi­rect response models differ from other models in Phoenix in that they use a PK model to predict con­centrations, and then use these concentrations as input to the indirect PD response model.

Model 51

Inhibition of input.

IR51.png 

indirectmodelcalc01154.png 

Estimated parameters
Kin     Kout     IC50 

Model 52

Inhibition of output.

IR52.png 

indirectmodelcalc01156.png 

Estimated parameters
Kin     Kout     IC50 

Model 53

Stimulation of input.

IR53.png 

indirectmodelcalc01158.png 

Estimated parameters
Kin     Kout     EC50     Emax

Model 54

Stimulation of output.

IR54.png 

indirectmodelcalc01160.png 

Estimated parameters
Kin     Kout     EC50     Emax
Model notation

Term

Definition

R

Measured response to a drug.

kin 

The zero-order constant for the production of response.

kout 

The first-order rate constant for loss of response.

Cp

Plasma concentration of a drug.

Ce

Drug concentration at the effect site.

IC50 

Drug concentration required to produce 50% of the maximal inhibition.

Emax

Maximum drug effect.

EC50 

Concentration in plasma that achieves 50% of predicted maxi­mum effect in an Emax model.

 

Last modified date:6/26/19
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