This example demonstrates some frequently used calculations, including compu-tation of:
» Fraction of drug absorbed using IV and oral data.
» Metabolite to parent drug ratios.
» Change from baseline to be used in AUC calculations.
Computing ratios
Phoenix can compute derived parameters as ratios of modeling output parame-ters. This functionality has been designed specifically for the computation of F (fraction of oral dose absorbed) and for the calculation of metabolite to parent drug ratios.
This example will demonstrate the computation of F. Metabolite to parent drug ratios would be calculated in the same manner.
Two data sets are needed for this example: one with AUC from IV data for 24 subjects, and another with AUC from oral data from the same 24 subjects. These data sets are provided in the Phoenix example subdirectory as IV.csv and Oral.csv.
The example opens these two data sets, merges them into one data set, com-putes F for each subject, then computes summary statistics for F.
Create the project and import the data
1. Select File > New Project to create a new project. A new project is created in the Object Browser.
Import the data sets:
Note: Select multiple files at once in the Open File(s) dialog by pressing the CTRL key and using the pointer to select the files.
1. Select File > Import or click the Import button. The Open File(s) dialog is displayed.
2. Navigate to the Phoenix examples directory, which by default is located at C:\Program
Files\Pharsight\Phoenix\applica-tion\Examples.
3. Select IV.csv and click Open.
The Worksheet Import Options dialog is displayed. The dialog is used to assign options for how the data are imported and presented.
4. Click Finish. The data set is added to the project’s Data Folder.
5. Import the data set Oral.csv and click Open.
6. Click Finish. The data set is added to the project’s Data Folder.
Data sets in CSV (Comma Separated Value) format are added to the Data folder as worksheets.
7. View the data sets by selecting them in the Data folder to display them in the Grid tab, which is located in the right viewing panel.
Merge the two data sets
1. Select the workflow in the Object Browser and then select Insert > Data >
Join Worksheets.
The Join Worksheets object is added to the workflow in the Object Browser.
2. Map the data set IV as an input source for the Join Worksheets object:
• Use the pointer to drag the IV worksheet from the Data folder to the Join Worksheets object’s Worksheet 1 Mappings panel.
OR
• In the Join Worksheets Worksheet 1 Mappings panel click the Select source button to open the Select Object dialog.
• Select the IV worksheet and click Select.
3. Repeat Step 2 to map Oral to the Join Worksheets object’s Worksheet 2 Mappings panel.
The IV and Oral data sets are mapped to the Join Worksheets object.
4. Use the option buttons in the Worksheet 1 Mappings panel to map the data types to the following contexts:
• Map Subject to the Sort context.
• Map Form to the Source Column context.
• Map AUC to the Source Column context.
5. Use the option buttons in the Worksheet 2 Mappings panel to map the data types to the following contexts:
• Map Subject to the Sort context.
• Map Form to the Source Column context.
• Map AUC to the Source Column context.
6. Click the Execute button. The results are displayed on the Results tab.
Join Worksheets Result worksheet
7. Copy the joined worksheet to the Data folder.
• Right-click the Join Worksheets object’s Result worksheet and select Copy
The Result worksheet is added to the project’s Data folder and renamed Result from Join Worksheets.
Calculate F (fraction of oral dose absorbed):
1. Select the workflow in the Object Browser and then select Insert > Data >
Data Wizard.
The Data Wizard object is added to the workflow in the Object Browser.
2. On the Options tab. in the Action menu, select Transformation.
3. Click the Add button on the Options tab.
4. Map the data set Result from Join Worksheets as an input source for the Data Wizard (Step 1: Transformation):
• Use the pointer to drag the Result from Join Worksheets worksheet from the Data folder to the Column Transformation object’s Main Mappings panel.
OR
• In the Column Transformation Main Mappings panel click the Select source button to open the Select Object dialog.
• Select the Result from Join Worksheets worksheet and click Select.
The Result from Join Worksheets data set is mapped to the Column Trans-formation object.
5. Arithmetic is automatically selected in the Transformation Type menu. Do not change this setting.
6. Select x/y in the Transformation menu.
7. In the New Column Name field type Fraction.
8. Use the option buttons in the Main Mappings panel to map the data types to the following contexts:
• Map AUC_1 to the Y Column context.
• Map AUC_2 to the X Column context.
9. Click the Execute button. The results are displayed on the Results tab.
10.Copy the transformed worksheet to the Data folder.
11.Right-click the Column Transformation object’s Result worksheet and select Copy to Data Folder.
The Result worksheet is added to the project’s Data folder and renamed Result from Data Wizard.
Calculate descriptive statistics
1. Select the workflow in the Object Browser and then select Insert > NCA and Toolbox > Descriptive Stats.
The Descriptive Stats object is added to the workflow in the Object Browser.
2. Map the data set Result from Data Wizard as the input source for the Descriptive Stats object:
• Use the pointer to drag the Result from Data Wizard worksheet from the Data folder to the Main Mappings panel.
OR
• In the Descriptive Stats Main Mappings panel click the Select source button to open the Select Object dialog.
• Select Result from Data Wizard and click Select.
The Result from Data Wizard data set is mapped to the Descriptive Stats object.
3. Use the option buttons in the Main Mappings panel to map the data types to the following contexts:
• Map Fraction to the Summary context.
• Leave all other data types mapped to None.
Use the Options tab to specify settings for the Descriptive Stats options. The Options tab is located underneath the Setup tab.
4. Select the Confidence Interval check box. The default setting for the Confi-dence Interval is 95%. Do not change this setting.
5. Select the Number of SD check box. The default setting for the number of standard deviations is 1. Do not change this setting.
6. Click the Execute button. The results are displayed on the Results tab.
The Statistics worksheet results are shown below: