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Simultaneous 3 compartment model plasma plus tissue


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#1 vk_pharmacy

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Posted 21 January 2019 - 01:47 AM

Hi,

 

I have plasma as well as tissue concentration (Liver and brain) and I would like to develop 3 compartment model for the drug using all three concentration. 

 

Could anyone tell how to do in Phoenix NLME? How to prepare a data file and how to add 3 observation in the model?  It would be great if someone shares the datafile preparation and show how to map in NLME.



#2 Simon Davis

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Posted 21 January 2019 - 06:49 AM

Morning, This should be fairly straightforward, at least in model definition. I think it would be easier to have the measurements for each compartment as their own column of data, e,g, c_plasma, c_brain, c_liver. Choose a base model e.g. 2 compartments and then once you have chosen "edit graphical" you can right click in your model to add extra observations and compartments as required.

I would look at the NLME examples guide, to become more familiar with the model building e.g. Graphically create a peripheral elimination model (page 177 in v8.1 documentation)

and also look at some of the recorded PML school webinars e.g. https://support.cert...onal-antibodies.

Try and that and if you get stuck post the project file back here and we can try to advise further.

Simon.

Edited by Simon Davis, 21 January 2019 - 08:33 AM.


#3 smouksassi1

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Posted 21 January 2019 - 03:08 PM

keep in mind that the compartmental models do not have physiological meaning except very few unique cases.

If you are really looking for a model representing Brain and Heart you need to go into PBPK and PML can be coded that way you can make your PBPK a simplified one depending on your needs.

As Simon mentioned you can have sperate columns or your can have one column with a differentiator between the observations 

at a given time point you might have one type of observation only and that is fine you can leave cells empty Phoenix understand empty cells.

 

 

Hi,

 

I have plasma as well as tissue concentration (Liver and brain) and I would like to develop 3 compartment model for the drug using all three concentration. 

 

Could anyone tell how to do in Phoenix NLME? How to prepare a data file and how to add 3 observation in the model?  It would be great if someone shares the datafile preparation and show how to map in NLME.



#4 vk_pharmacy

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Posted 11 February 2019 - 07:51 PM

Thanks for your reply. I was able to fit my model.


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#5 sylim

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Posted 24 January 2021 - 08:37 PM

Hi,

 

If we use a compartmental model to describe plasma (mg/mL) and tissue concentrations (mg/g), how do we estimate volume of distribution of the tissue compartments? 

 

We use k12*V1=k21*V2 to derive V2 in a typical two-compartment model. In this case, V1 is central Vd in mL and V2 is "tissue compartment volume" and in a different unit, g. Can we simply add V2 as a parameter to be estimated? That would seem to make the estimation of k12 and k21 more difficult. 

 

Thanks, any advice or help is appreciated. 



#6 Simon Davis

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Posted 25 January 2021 - 11:42 AM

you may find parametising in clearance rather than micro constants gives more stable solutions.






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