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Continuous infusion and dialysis

infusion dialysis

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#1 marie.simeckova

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Posted 14 April 2021 - 08:19 AM

Hello,

 

I have two questions please:

  • Is there a way in WNL how to analyse PK parameters (mainly AUC, volume of distribution and total clearance) when the patients have a continuous infusion of the study drug - starting before the first PK sample, ending after the last PK sample? Moreover, the dose of the drug in the infusion is changing.
  • Could I calculate dialytic clearance in WNL?

Thanks a lot for your answer.

 

Marie



#2 bwendt@certara.com

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Posted 14 April 2021 - 10:06 AM

Dear Marie,

 

for continuous infusion data you could use NCA Model 202 in Phoenix WinNonlin to get estimates for AUC, Vd and Cl. However, when the dose of the drug is changing during this period, I would recommend compartmental modeling, e.g. a Phoenix Model to get better estimates for volume and clearance.

Wrt dialytic clearance, you can estimate the required parameters in Phoenix WinNonlin (either through NCA or Phoenix Model) and use a Data Wizard object with a Transformation step to calculate dialytic clearance.

 

Let me know if this helps or if you have further questions.

 

Bernd



#3 marie.simeckova

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Posted 16 April 2021 - 03:09 PM

Dear Bernd,

 

Thank you for the quick answer. However, I am still confused, I do not know how to implement the NCA Model 202 for the infusion. It seems to me that the model assumes only 1 dose of infusion and this infusion should stop before the plasma sampling. I would be grateful if you can me explain more details or write where I can find the details.

 

I can compute the AUC but don't know what to do with Vd and Cl.

 

There are the data for a patient: 

 

Id Time         Concentration

1  29.08333  13

1  31.08333  11

1  33.08333  11

1  37.08333    9

 

And  the infusion details (the infusion actually started hours before, the time is the time since the start of it; the infusion does not stop, the length is the period between the two time points): 

 

Id   Time         Length     Dose 

1    8.616667 21.13333  13.5

1  29.75         48.75          9

1  78.5           16.83333    4.5

 

When I run the NCA model 202, it seems to me that for each patient, the model uses only the last dose, which is actually after the last PK concentration sampling and so there are 0 points used and the model does not work.

 

I would appreciate any hints or ideas.

 

Marie


Edited by marie.simeckova, 16 April 2021 - 03:10 PM.


#4 bwendt@certara.com

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Posted 16 April 2021 - 04:52 PM

Dear Marie,

 

please find project file attached where I have configured a Phoenix Model object and an NCA object with your data. Given the sparseness of your data the estimation is not great, but as you can see, Phoenix Model and NCA gives rather close estimates for each of clearance, volume and AUC:

 

Phoenix Model:

 

1. Clearance and Volume:

IVinfusion1.png

 

2. AUC:

IVinfusion2.png

 

NCA:

IVinfusion3.png

 

Let me know if there are questions.

 

Bernd

 

Attached File  IV_variable_infusion.phxproj   750.7KB   13 downloads

 



#5 marie.simeckova

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Posted 17 April 2021 - 08:01 AM

Dear Bernd,

 

thanks a lot, unfortunatelly, I can't load your project, the log is in the attachment.

 

Maybe the problem is that I have an older version, although it was instaled half a year ago - version 8.3.1.5014. I will contact out IT on Monday whether we can update. Or do you have some other idea?

 

Marie

Attached Files


Edited by marie.simeckova, 17 April 2021 - 08:50 AM.


#6 bwendt@certara.com

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Posted 17 April 2021 - 12:31 PM

Dear Marie, please ignore the warning, you should be able to load the project file despite the warning. It has been created with Phoenix 8.3.2.

Bernd

#7 marie.simeckova

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Posted 19 April 2021 - 05:25 AM

Dear Bernd,

 

that is not warning, that is an error and the project is not loaded. It shows "There were errors in loading objects.  For details, see the Phoenix log file by selecting Help | View Log" and "There was an error loading the project file c:\\..."

 

The projects is not loaded and I have no idea how to change it (I have tried).

 

Marie



#8 bwendt@certara.com

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Posted 19 April 2021 - 02:17 PM

Dear Marie,

 

I have prepared a new project file, see attached.

 

Bernd

 

Attached File  IV_infusion_variable.phxproj   956.11KB   11 downloads



#9 marie.simeckova

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Posted 21 April 2021 - 09:08 PM

O great, thanks a lot Bernd, the project file is very helpful.

 

One more question: You have chosen a model in your project. Can I find somewhere a text about the model choice, its mathematical description and description of the parameters? I mean a guide, tutorial, help pages...



#10 bwendt@certara.com

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Posted 23 April 2021 - 09:33 AM

Dear Marie,

 

I have used a standard 1-compartment model with IV Infusion input, which is the simplest model you can start with. You only need to estimate two parameters: Volume and Clearance.

You will find descriptions about this model in all text books around pharmacokinetics, for example:

GABRIELSSON, Johan; WEINER, Dan. Pharmacokinetic and Pharmacodynamic Data Analysis.

 

Bernd







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