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Need assistance with a 3 compartment model


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#1 John CK Lai

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Posted 13 August 2018 - 03:10 PM

Hi,

 

Can someone assist me in fitting the following extended release plasma conc time data?  Literature suggested that the IR profiles (and IV) follows a 3 compartment model.  I tried to fit it but I was not successful. :angry:

 

Thank you v much.

John

 

 

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#2 bwendt@certara.com

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Posted 13 August 2018 - 03:21 PM

John,

 

why do you want to fit a 3-compartment model? 

Please find a project file attached where I tried 1-, 2- and 3-compartments on your data. As you can see from the Theta tables the data only justifies one compartment, with tlag parameter. 

 

Bernd

 

 

Attached File  John.phxproj   938.63KB   352 downloads



#3 bwendt@certara.com

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Posted 13 August 2018 - 03:23 PM

Is this simulated data? Or, can you give the reference?

 

Bernd



#4 bwendt@certara.com

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Posted 13 August 2018 - 04:04 PM

Absorption is not 1st order - could be flip-flop kinetics?



#5 John CK Lai

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Posted 13 August 2018 - 04:04 PM

Is this simulated data? Or, can you give the reference?

 

Bernd

Thank you Bernd.  It's real data from an extended release drug delivery system.  The reason I attempted 3 compartment because published IV data suggested 3 compartment model. 



#6 John CK Lai

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Posted 13 August 2018 - 04:06 PM

Absorption is not 1st order - could be flip-flop kinetics?

Osmotic pump delivery ER system.  0 order release kinetics (I hate it... I recall a paper which discussed the model for a osmotic pump delivery , something like a infusion derived model.)

 

thanks

John



#7 bwendt@certara.com

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Posted 14 August 2018 - 11:43 AM

John,

 

thanks, this is valuable information. Please find attached an updated project file with:

 

1. graphical model - here I tried to rebuild the osmotic pump delivery. Fit did not improve and precision of parameter estimates cannot be estimated.

 

2. textual model with new distributed delay function - this new function is perfectly suited for this type of problem where you model absorption delays. 

 

Hope, this is helpful.

 

Bernd

 

Attached File  John.phxproj   1.58MB   352 downloads






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