n Transit compartment single distribution compartment PK absorption model in simbiology
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I have built a n-transit compartment with single distibutional pharmacokinetic absorption model using SimBiology. This model is based on the TRANSIT model descibed in the following publication: Savic, R.M., Jonker, D.M., Kerbusch, T. et al. J Pharmacokinet Pharmacodyn (2007) 34: 711. https://doi.org/10.1007/s10928-007-9066-0
I chose to start by loading a one compartment absorption model with Clearance parmaeterization (macro parameters) and then modified the absorption reaction equation as n transit compartment that is based on an analytical solution to determine the transit compartment number as a continuous variable (not an interger).
analytical solution for number of compartments:
![n analytical solution.PNG](https://www.mathworks.com/matlabcentral/answers/uploaded_files/214672/n%20analytical%20solution.png)
Single distribution compartment ODE:
![nTransit 1Comp ODE.PNG](https://www.mathworks.com/matlabcentral/answers/uploaded_files/214673/nTransit%201Comp%20ODE.png)
transform of ODE for numerical stability when n is large:
![ODE transform.PNG](https://www.mathworks.com/matlabcentral/answers/uploaded_files/214674/ODE%20transform.png)
Attache is a report summarizing how I defined the model in simbiology.
I am not sure if I have used the wrong syntax but I am seeing negative cincentrations at the first simulated timepoints as shown by this simulation plot:
![sim.PNG](https://www.mathworks.com/matlabcentral/answers/uploaded_files/214675/sim.png)
The simulation should be a gradual absorption phase in contrast to typical tlag absorption models that are in the simbiology PK model library.
Cheers,
Dan
2 件のコメント
Arthur Goldsipe
2019 年 4 月 18 日
I have two comments/questions:
1) What question are you asking use? I'm hoping you can formulate something fairly specific.
2) If you want us to debug your model, could you could attach the actual model, either as a MAT file or an SBPROJ file?
回答 (1 件)
Wojciech Krzyzanski
2019 年 4 月 19 日
Dear Dan,
For a positive input to the Aa compartment and 0 initial value (Aa(0)=0), your solultion Aa(t) should be always positive. Your simulated absorption curve implies that you have ODE solver issues. Since you mentioned that the number of transit compartments is large, I think this is a stiffness problem, and your ODE solver is not suited for stiff equations. Did you get negative Aa for smaller n? Stiffness can occur for large ka as well.
Regards,
Wojciech
2 件のコメント
Jeremy Huard
2019 年 4 月 25 日
編集済み: Jeremy Huard
2019 年 4 月 26 日
Hi Daniel,
the equation defining the transit compartment is only valid for a single bolus.
But you can modify it for repeated dosing by replacing 'time' in the equation by the time from dosing as suggested here: https://dx.doi.org/10.1128%2FAAC.00461-07
In SimBiology you would need to add an event that stores the time of dosing. If your dose amount is constant, this is all you would need to do. If your dose amount depends on a model parameter, you can modify Dose in this event.
I have implemented this in your model (see attached file).
Edit: This was the wrong URL. I have corrected it.
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