Indirect block

PK/PD models with stimulation or inhibition of the indirect response formation or degradation can be created using this block.

Insert an Indirect block by selecting Insert > PD > Indirect from the right-click menu.

The Indirect block contains five input nodes and one output node. The input nodes are made available depending on the options that are selected in the Structural tab. If an input node cannot be used, it is marked with an X.

The input nodes on the Indirect block can be connected to output nodes on PK compartments, observation blocks, PD blocks, and parameter blocks. Once an output node is connected, its name cannot be changed.
Insert an Indirect block by selecting Insert > PD > Indirect from the right-click menu.

To specify Indirect block options

Use the pointer to select an Indirect block.
In the Ind field, enter a name for the Indirect block or use the default.
In the Indirect menu select the indirect model type:

Stim. Limited (limited stimulation of input)
Stim. Infinite (infinite stimulation of input)
Inhib. Limited (limited inhibition of input)
Inhib. Inverse (inverse inhibition of input)
Stim. Linear (linear stimulation of input)
Stim. Log Linear (logarithmic and linear stimulation of input)

Use the Indirect menu options to select a model in which the response formation (build-up) or degradation (loss) is stimulated or inhibited by increased concentrations. The default response setting is the build-up of the response, or the production of the response.

Click Build-up multiple times to toggle between the options:

Build-up: Changes the statement for the Ke parameter to Kin.
Loss: Changes the statement for the Ke parameter to include Kin-Kout, where Kin is the zero-order input rate constant and Kout is the first output rate constant.

Click no Exponent multiple times to toggle between the options:

no Exponent: Removes the exponent from the effect statement.
Exponent: Adds the exponent Gamma to the effect statement.

In each parameter field, enter names for each parameter or use the defaults.

Each parameter corresponds to an input node on the Indirect block. Possible Indirect parameters include:

Kin: Zero-order turnover rate for the production of a response.
Kout: Fractional turnover rate.
Emax: Maximum drug induced effect.
Imax: Maximum drug induced inhibition.
EC50: Concentration at 50% of maximal effect.
IC50: Concentration producing 50% of maximal inhibition.
Gam: Exponent parameter.