Semicompartmental modeling was proposed by Kowalski and Karim (1995) for modeling the temporal aspects of the pharmacokinetic-pharmacodynamic relationship of drugs. Their model was based on the effect-site link model of Sheiner, Stanski, Vozeh, Miller and Ham (1979) to estimate effect-site concentration Ce, but uses a piecewise linear model for plasma concentration Cp rather than specifying a PK model for Cp. The potential advantage of this approach is reducing the effect of model misspecification for Cp when the underlying PK model is unknown.
Use one of the following to add the object to a Workflow:
Right-click menu for a Workflow object:
New > NonCompartmental Analysis > Semicompartmental Modeling.
Main menu:
Insert > NonCompartmental Analysis > Semicompartmental Modeling.
Right-click menu for a worksheet:
Send To > NonCompartmental Analysis > Semicompartmental Modeling.
Note:To view the object in its own window, select it in the Object Browser and double-click it or press ENTER. All instructions for setting up and execution are the same whether the object is viewed in its own window or in Phoenix view.
User interface description
Results
Semicompartmental calculations
Semicompartmental model example
Main Mappings panel
Options tab
Plots tab (See the “Plots tab” description in the NCA section.)
Use the Main Mappings panel to identify how input variables are used in the Semicompartmental object. Semicompartmental modeling requires a dataset containing time and concentration data, and sort variables to identify individual profiles. Required input is highlighted orange in the interface.
None: Data types mapped to this context are not included in any analysis or output.
Sort: Categorical variable(s) identifying individual data profiles, such as subject ID in a semicompartmental analysis. A separate analysis is performed for each unique combination of sort variables.
Time: The relative or nominal dosing times used in a study.
Concentration: The measured amount of a drug in blood plasma.
Effect: The measured effect data.
The Options tab allow users to select the computation method and the Ke0 value.
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In the Computation Method menu, select the method Phoenix uses to perform the semicompartmental analysis.
Linear uses a linear piecewise PK model.
Log uses a log-linear piecewise PK model.
Linear/Log start with linear to Tmax and then log-linear after Tmax; this is also the default option.
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In the Ke0 field, type the value for the equilibrium rate constant.
The Semicompartmental model object generates four charts, one worksheet, and one text file.
Up to four plots are created for each profile. Each profile’s plot is displayed on its own page in the Results tab. Click the page tabs at the bottom of each plot panel to view the plots for individual profiles. If drug effect data is included in the dataset, Effect vs Ce and Effect vs Cp plots are also created.
Ce vs Time: Estimated effect site concentration vs. time.
Cp vs Time: Plasma concentration vs. time.
Effect vs Ce: Drug effect vs. the estimated effect site concentration.
Effect vs Cp: Drug effect vs. plasma concentration.
A text file called Settings is also created. It lists the user-specified settings in the Semicompartmental object
The Semicompartmental object creates a worksheet called Results. This worksheet contains: sort variables (if any are used), time points used in the study, drug concentration levels in blood plasma, Ce (estimated effect site concentration), effect data (if included). Any units associated with the time and concentration columns in the input data are carried through to the semicompartmental modeling output.
