Modeling defectuous transporter

Fortran model files with standardized descriptions.
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pabill
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Joined: Tue Nov 25, 2014 9:05 am

Modeling defectuous transporter

Post by pabill » Tue Nov 25, 2014 10:13 am

Hi,
I would like to make an ODE for a model with 3 compartments.
The first compartment is my Nbolus.
The second is my drug in plasma.
To enter the intracellular (and last) compartment the drug has to be carried by an active transporter.
With a "classical" ODE such as
XP(1) = -Ka*X(1)
XP(2) = Ka*X(1) - K20*X(2) - K23*X(2) + K32 *X(3)
XP(3) = K23*X(2) - K32 *X(3) -K30*X(3)
I get a poor iPred for my intracellular drug (R²#0.6), moreover my K32 let clearly appear 2 subpopulations with a range of 100 !
I am pretty sure that there is a loss of the activity of the transporter in some patients.
I also tried to use MM equation unsuccessfully.
Has somebody already encounter this problem or has any idea of a new ODE ?
Regards

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mneely
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Re: Modeling defectuous transporter

Post by mneely » Wed May 27, 2015 10:23 am

It's interesting that you have a K30 term. Is it being metabolized intracellularly? It would be hard to distinguish that kinetically from drug moving back out of the cell into plasma, since the amounts in cells are so small relative to plasma. What if you either take out K30 or K32?

pabill
Posts: 4
Joined: Tue Nov 25, 2014 9:05 am

Re: Modeling defectuous transporter

Post by pabill » Fri Aug 19, 2016 5:26 am

Thank you for your answer. Yep K30 is related to both intracellular metabolism and DNA incorporation. Taking out K30 and K32 values improves the model. However this values are really meaningful thus rending this approximation quite hard to justify...

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