Phoenix WinNonLin

Connecting

• How to connect to the windows server

Instructions

• Pheonix WinNonLin Help
  1. Quick TourPDF Version
  2. PharmacokineticsPDF Version
  3. Non-compartment AnalysisPDF Version
     • User Guide on NCA (PDF)-Extra information

Tentative Pheonix WinNonLin Project

Task #1-Learn WinNonLin

Click for instructions here. You can stop at "Execute noncompartmental analysis"

1. Make an MS Word docx document called Task01-Learning_Phoenix_WinNonLin.docx
2. On the first page, describe what each of the abbreviations mean.
3. Open Phoenix WinNonLin
4. Create a new project called Task01-Learning_Phoenix_WinNonLin.phxproj
5. Import dataset based on your student number such as Task01-Student01.dat
6. Make a XY plot of your data (e.g., Task01-Student01.dat)
7. Add the XY plot to one of the pages of your MS Word docx: Task01-Learning_Phoenix_WinNonLin.docx
8. Make a table of your data.
9. Add the table to one of the pages of your MS Word docx: Task01-Learning_Phoenix_WinNonLin.docx
10. In Task01-Learning_Pheonix_WinNonLin.docx, and answer the following questions on the last page (Simple definitions please. Does not have to be complicated mathematics.):
    1. What is the difference between mean, harmonic mean, and geometric mean?
    2. What is the difference between standard deviation, standard error and pseudo standard deviation?
    3. What does coefficient of variation (CV%) mean in the context of this data?
    4. What does interquartile range (IQR) mean in terms of pharmacokinetics?
11. Send Task01-Learning_Pheonix_WinNonLin.docx and Task01-Learning_Pheonix_WinNonLin.phxproj to me. You can email me directly from the remote desktop.

Tips, Additional Instructions, and Information

1. The instructions are pretty good. The task takes about 1-2 hours.
2. I recommend doing the example first.
3. Change "Map Subject to the Stratification Row context." to "Map Subject to the Stratification Column context." because it is easier to read in MS Word 2013.
4. The path is wrong in the instructions. The path should be C:\Program Files (x86)\Pharsight\Pheonix\application\Examples\Bguide1.dat
5. This might be confusing, use the Microsoft Word 2013 that is on the Remote Desktop
6. Right click on Figures to Copy them into Microsoft Word 2013
7. Right click under Result Tables → Tables on the right. Then click Export... and save it somewhere where you can find it in html format. The default is table.html.
8. Open the html file as a separate document and copy the table into the main document.
   1. You can find a lot of questions by going into Google and typing, "meaning of standard error" for the answer to question #2.
9. If you are using Windows 10, you can paste directly back and forth between the Remote Desktop and your computer.
10. Useful Links
    1. https://math.usask.ca/~laverty/S244/Lecture4.pdf

Student Data

• Task01-Student01.dat
• Task01-Student02.dat
• Task01-Student03.dat
• Task01-Student04.dat
• Task01-Student05.dat
• Task01-Student06.dat
• Task01-Student07.dat
• Task01-Student08.dat
• Task01-Student09.dat
• Task01-Student10.dat
• Task01-Student11.dat

Task #2-Dr. Roberts' Attempt to Fit Pharmacokinetic Parameters

• I like very detailed instructions because the instructions make it easier for me to go back where I was.

1. Click
2. File → New Project or Control + N
3. I named the file "Dr Roberts PK Project"
4. Downloaded Task02-Student10.csv, since I am Student10
5. Right Click on Data, which is on the left side and right click import and open the data that you downloaded.
   • If you did it correctly, it should look like: Click to enlarge
6. Select the Radio Button for Has units row. I missed it the first time.
   • If you did it correctly, it should look like:
7. Click
   • If everything worked correctly, it should look like: Click to enlarge
8. Right-click Workflow in the Object Browser and select New > Plotting > XY Plot.
   • It should look like this: Click to enlarge
9. Double click on the XY Plot
   • It should look like this: Click to enlarge
10. Drag the Task02_Student10 worksheet to the XY Plot window. This can be a little tricky. It might take you a couple tries.
    • It should look like this: Click to enlarge
11. Leave Subject mapped to the None context. Map Time to the X context. Map Conc to the Y context.
    • It should look like this: Click to enlarge
12. Click the
    • If you did it correctly, it should look like: Click to enlarge
13. In the Options tab below the plot, select Axes > Y from the menu tree.
14. Select the Logarithmic option button in the Scale area. Leave the logarithmic base set to 10.
    • If you did it correctly, it should look like: Click to enlarge
    • The final graph should look like: Click to enlarge
15. Right Click > New > Modeling > Least-squares Regression Models > PK Model
    • If you did it correctly, it should look like: Click to enlarge
16. I dragged Task02_Student10 data into the PK model
    • If you did it correctly, it should look like: Click to enlarge
17. Map Subject to the Sort context. Leave Time mapped to the Time context. Map Conc to the Concentration context.
    • If you did it correctly, it should look like: Click to enlarge
18. In the Model Selection tab below the Setup panel, check the Number 3 model checkbox.
    • If you did it correctly, it should look like: Click to enlarge
19. Select the Dosing panel in the Setup tab. Check the Use Internal Worksheet checkbox.
    • If you did it correctly, it should look like: Click to enlarge
20. Click
    • If you did it correctly, it should look like: Click to enlarge
21. Put in a time of 0 and a dose of 2.
    • If you did it correctly, it should look like:
22. In the Weighting/Dosing Options tab below the Setup panel, type ug in the Unit field.
    • If you did it correctly, it should look like: Click to enlarge
23. In the Parameters option menu, select the User Supplied Initial Parameter Values option.
    • If you did it correctly, it should look like: Click to enlarge
24. Select the Initial Estimates tab, check the Internal Worksheet Box and click OK when the dialog comes up.
    • If you did it correctly, it should look like: Click to enlarge
25. Go to the XY Plot and select a point that is half way on the absorption phase. It should look something like:
    • The two values are 0.4 and 0.013, which represent the time and the concentration. An approximate absorption rate constant (k_a) = 1/0.4 = 2.5 hr^-1.
26. Go to the XY Plot and select a point that is half way on the elimination phase. It should look something like:
    • I could not get the numbers to show up, but the half way point is about 12.5 hrs. An approximate elimination rate constant (k_e) = 1/12.5 = 0.08 hr^-1.
27. Now, let us go back to the model:
    • K01 is the k_a and K10 is the k_e.
28. Go back and Select the Initial Estimates tab.
29. For K01, I put 2.5 hr^-1 and for K10, I put 0.08 hr^-1, but what is the V_F term? The V_F term is in units of μg/(ng/mL). That is very strange. Let us simplify.
    • μg/(ng/mL) = μg/(μg/L)> μg cancel out, which leaves us liters. Why don't they simplify in the first place? I have no idea. In the original example, they have 0.25 L. Let us try that and see what happens.
30. For K01, I put 2.5 hr^-1, for K10, I put 0.08 hr^-1 and for V_F, I put 0.25 L like the example. This is what I have: Click to enlarge.
31. Right click on Task02_Student10 > Send To > Modeling > Maximum Likelihood Models
    • If you did it correctly, it should look like this: Click to enlarge.
32. Check ML Model under Workflow
    • If you did it correctly, it should look like this: Click to enlarge.
33. In the Structure tab, uncheck the Population? box.
    • If you did it correctly, it should look like this: Click to enlarge.

Task #2-Fit Pharmacokinetics

Click for instructions here. You can stop at "Simulation and study design of PK models example"

1. Make an MS Word docx document called Task02-Fit_Pharmacokinetics.docx
2. On the first page of Task02-Fit_Pharmacokinetics.docx put a list of abbreviations and what they mean: tvKa, tvV, tvKe, stdev0, K01, K10, etc.
3. Open Phoenix WinNonLin
4. Create a new project called Task02-Fit_Pharmacokinetics.phxproj
5. Import dataset based on your student number such as Task02-Student01.csv.
6. Put he six plots on separate pages of Task02-Fit_Pharmacokinetics.docx
7. Put the output data ⇒ results on a separate page of Task02-Fit_Pharmacokinetics.docx
   1. These should have values for tvKa, tvV, tvKe, stdev0, K01, K10
8. In Task02-Fit_Pharmacokinetics.docx, describe what your results mean in a descriptive language.
9. Send Task02-Fit_Pharmacokinetics.docx and Task02-Pharmacokinetics.phxproj to me.

Tips and Notes

• The path of the example is wrong in the instructions. The path should be C:\Program Files (x86)\Pharsight\Pheonix\application\Examples\

Student Data

• Task02-Student01.csv
• Task02-Student02.csv
• Task02-Student03.csv
• Task02-Student04.csv
• Task02-Student05.csv
• Task02-Student06.csv
• Task02-Student07.csv
• Task02-Student08.csv
• Task02-Student09.csv
• Task02-Student10.csv
• Task02-Student11.csv

Task #3-Non-Compartment Analysis

Click for instructions herePDF Version

1. Make an MS Word docx document called Task03-Non-Compartment_Analysis.docx
2. On the first page of Task03-Non-Compartment_Analysis.docx, put the following parameters:
   1. Tau, Rsq_adjusted, MRTINF_pred, TimeLow, TimeBetween, TimeHigh, TimeInfBetween, Lamda Z
   2. Explain them in simple language. You can usually find them through a Google search.
3. Open Phoenix WinNonLin
4. Create a new project called Task03-Non-Compartment_Analysis.phxproj
5. Import dataset based on your student number such as Task03-Student01.dat.
6. Put a table of the results of one of the patients onto a page in Task03-Non-Compartment_Analysis.docx
7. Put the NCA plot for the same patient onto a page of Task03-Non-Compartment_Analysis.docx
8. Put the Final Parameters Pivoted onto a page of Task03-Non-Compartment_Analysis.docx
9. Put the Ratios Differences onto a page of Task03-Non-Compartment_Analysis.docx
10. In Task03-Non-Compartment_Analysis.docx, describe what your results mean in a descriptive language.
11. Send Task03-Non-Compartment_Analysis.docx and Task03-Non-Compartment_Analysis.phxproj to me.

Tips and Notes

• Example data does not work. Your student data should work the same as the example.
• Read the instructions very carefully. This section took me a while to get through.

Student Data

• Task03-Student01.dat
• Task03-Student02.dat
• Task03-Student03.dat
• Task03-Student04.dat
• Task03-Student05.dat
• Task03-Student06.dat
• Task03-Student07.dat
• Task03-Student08.dat
• Task03-Student09.dat
• Task03-Student10.dat
• Task03-Student11.dat

Task #4-Bioequivalence

Click for instructions herePDF Version

1. Make an MS Word docx document called Task04-Bioequivalence.docx
2. On the first page describe the following abbreviations in easy to understand language:
   1. ln(AUClast), Hypothesis, Numer_DF, Denom_DF, F_Stat, P_value, CI_90_Lower, CI_90_Upper
3. In simple language, describe what a 2x2 and a 2x4 crossover study.
4. Open Phoenix WinNonLin
5. Create a new project called Task04-2x2-Bioequivalence.phxproj
6. Import dataset based on your student number such as Task04-2x2-Student01.csv.
7. Put a copy of the Average Bioequivalence worksheet on a page of Task04-Bioequivalence.docx
   1. Label and underline with 2x2 Crossover
8. Put the Partial Tests and Sequential Tests worksheets on a page of Task04-Bioequivalence.docx
   1. Label and underline with 2x2 Crossover
9. Create a new project called Task04-2x4-Bioequivalence.phxproj
10. Import dataset based on your student number such as Task04-2x4-Student01.csv
11. Put a copy of the Average Bioequivalence worksheet on a page of Task04-Bioequivalence.docx
    1. Label and underline with 2x4 Crossover
12. Put the Partial Tests and Sequential Tests worksheets on a page of Task04-Bioequivalence.docx
    1. Label and underline with 2x4 Crossover
13. Put the Population Individual worksheet on a page of Task04-Bioequivalence.docx
    1. Label and underline with 2x4 Crossover
14. In Task04-Bioequivalence.docx, describe what your 2x2 and 2x4 crossover study mean in a descriptive language.

Tips and Notes

• The path of the example is wrong in the instructions. The path should be C:\Program Files (x86)\Pharsight\Pheonix\application\Examples\
• Go through the example first.
• For the 2x2 Crossover, the Random Effects model is supposed to be Subject(Sequence) and the Type is Variance Components. When it was not set to this, WinNonLin crashed.

Student Data

2x2 crossover

• Task04-2x2-Student01.csv
• Task04-2x2-Student02.csv
• Task04-2x2-Student03.csv
• Task04-2x2-Student04.csv
• Task04-2x2-Student05.csv
• Task04-2x2-Student06.csv
• Task04-2x2-Student07.csv
• Task04-2x2-Student08.csv
• Task04-2x2-Student09.csv
• Task04-2x2-Student10.csv
• Task04-2x2-Student11.csv

2x4 crossover

• Task04-2x4-Student01.csv
• Task04-2x4-Student02.csv
• Task04-2x4-Student03.csv
• Task04-2x4-Student04.csv
• Task04-2x4-Student05.csv
• Task04-2x4-Student06.csv
• Task04-2x4-Student07.csv
• Task04-2x4-Student08.csv
• Task04-2x4-Student09.csv
• Task04-2x4-Student10.csv
• Task04-2x4-Student11.csv

Questions from Students

How do you guess the following parameters tvKa, tvV, tvKe?

1. A oral dosage will have and absorption phase and an elimination phase. The tvKa and the tvKe are pretty easy to estimate. The time where the amplitude of the absorption phase is half. Let us say that it is 0.2 hrs. Then a good guess for the tvKa would be 1/0.2 hrs or 5 hr^-1. Let us say that the half amplitude of the elimination phase is 2 hours. Then a good guess for the tvKe would be 1/2 hrs or 0.5 hr^-1.
2. With the third parameter, I would use the slider until it close.

Abbreviations

Pheonix WinNonLin	Classic WinNonLin	Likely Meaning	Guess (Y/N)
tvKa	K01	absorption rate constant (KA)	Y
tvV	V1_F	Volume of the central compartment?	Y
tvKe	K10	elimination rate constant (Ke)	Y
tvK12	K12	rate constant away from the central compartment to a peripheral compartment	Y
tvK21	K21	rate constant from the peripheral compartment to the central compartment	Y

Information

• Phoenix WinNonLin User Guide (PDF)
• Pheonix WinNonLin Abbreviations
• Exporting Tables and Graphs to MS Word