Least-Squares Regression Model calculations

Indirect Response models
Linear models
Michaelis-Menten models
Pharmacodynamic models
Pharmacokinetic models
PD output parameters in a PK/PD model
ASCII Model dosing constants
Parameter Estimates and Boundaries Rules
References

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 

indirectmodelcalc00564.png 

Estimated parameters:   Kin     Kout     IC50 

Model 52: Inhibition of output.

IR52.png 

indirectmodelcalc00566.png 

Estimated parameters:   Kin     Kout     IC50 

Model 53: Stimulation of input.

IR53.png 

indirectmodelcalc00568.png 

Estimated parameters:   Kin     Kout     EC50     Emax

Model 54: Stimulation of output.

IR54.png 

indirectmodelcalc00570.png 

Estimated parameters:    Kin     Kout     EC50     Emax

Model notation

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.


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