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Program Set-Up - Phoenix WinNonlin

A new project is started by selecting File > New Project. The project name can be changed to be more descriptive. Data can be entered using as a new Worksheet or by importing a file such as one in the csv (comma delimited) format.

Importing Data in a csv File

Figure 8.5.1 Importing Data in a csv File

This csv file included a header row with units. Check Has a header row and Has units in column header. Note the comma is selected as the Field Delimiter. Select the Data Set > Send To > Modeling > Least-Squares Regression Models > PK Model.

Choosing the Model and Mapping the Data

Figure 8.5.2 Choosing the Model and Mapping the Data

Under the Setup Tab choose Main to choose the PK model to be use and map the data columns to the correct heading. Time to Time and Concentration to Concentration. Here we have data collected after oral administration. Model 3 represents a one compartment model with no lag time and elimination is by a first order process. A diagram illustrating the model is shown in the right panel. If Modeling > Maximum Likelihood Models had been chosen the model could be represented graphically or textually for more flexibility.


Alternative Model Selection Options

Graphical Representation of a One Compartment Model after Oral Administration

Figure 8.5.3 Graphical Representation of a One Compartment Model after Oral Administration

Aa represents the amount in the dose compartment, A1 is the central compartment and A0 the elimination (urine) compartment. CObs is the observed concentration calculated as A1/V.

Textual Representation of a One Compartment Model after Oral Administration

Figure 8.5.4 Textual Representation of a One Compartment Model after Oral Administration (Phoenix Modeling Language [PLM])

The two deriv and the one urinecpt equation represent the differential equations for the A1, A0 and Aa components of the model. Concentration, C is defined as A1/V. The stparm equations map the typical (e.g. tvV) parameter values to the parameter values (V). The typical values are used in population pharmacokinetic analysis. The fixef equations provide initial estimates with lower and upper bounds. Here the bounds are not defined and the initial estimates are set to 1 before being determined during the curve stripping step.

The dose can be entered using the Setup > Dosing tab with Use Internal Worksheet checked. Data weighting can be chosen from the Weighting/Dosing Option tab below.

Dose and Weighting Options

Figure 8.5.5 Dose and Weighting Options

With a simple linear model we can have WinNonlin generate the initial parameter estimates using a curve stripping technique. Alternately the user can enter initial estimates after selecting User Supplied Initial Parameter Values.

Screenshot

Figure 8.5.6 Parameter Options

We are now ready to execute the PK model by clicking on the green arrow at the top.

Refer to the Help menu for more details. The Maximum Likelihood Models option is very flexible and a more complete description is beyond the scope of this page.

Screenshots are from Phoenix WinNonlin version 8.3.1 March 2021.


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This page was last modified: Friday, 2nd Apr 2021 at 4:54 pm


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