At the PML School we are trying to adopt a different way of modeling, not just simple translation, but a stepwise buildup of your model. We would start your model by building up the PK model from the built-in options, in this case a 3-compartment model with IV input and micro parametrization:
We would then switch to Graphical Model Builder and add a second dosepoint (e.g. IV Infusion), another compartment (the 4th one), you adjust the flows and parameter names between the compartments and end up with this:
This covers the PK part of you model. It is not quite clear how you add the first part of your code to the PK model. Perhaps you can add more description or a graphical representation of your model that would allow us to incorporate that into the model
The graphical model that I showed in my reply is more or less reflecting the tumor model that you showed in your picture. I have renamed the parameters in the graphical model and rearranged the compartments so that you can see the similarity:
If you have a dataset you might want to try the model that is included in the Phoenix project file. There are actually two Phoenix models, the PK model that I showed in my previous response and the tumor model where I simply changed the parameter names.
Thank you Bernd for your suggestions and support. It has helped me alot.
I have tried the model but it is not executing when I’m using dose instead of concentration.
I’m also attaching the Phoenix project file with the work done.
I have setup the Tumor Model as Simulation not as a simple fitting run. So I changes this under the Run Options tab.
There is no observation in the model, so I had to add a continuous observation and linked this object to the central compartment.This allows you to map your measured amounts in the Main input
I want to predict tumor concentration using this model so the driving force of the drug into the tumor is product of Plasma flow and Concentration in the central compartment and the drug follows 2 compartment model so I want this 2 compartment equation to be included while determining the concentration in the C3 compartment.
Cl3 (please see phoenix project file) = Q*C1 ; where
Q= plasma flow
C1= Ae^-at + Be^-bt
I’m attaching phoenix project file as well as an article for better understanding.
In addition, we introduced a lag time (Tlag) to account for a delayed appearance of the drug in the tumor. The Tlag was estimated by a curve feathering method and subtracted from the time profile of the tumor concentrations.
In PHX6.4 you can use only transit statement (transit compartments) which is closer to the distributed delay. AFAIK there’s no common way to get the simple delay in PHX6.4 (maybe some manipulations with sequence? Not sure…)
As I mentioned before this is something new in PHX7 (THX to developers!)
Please follow the PML User’s guide for description:
delay( , )
Outputs the value that had at the corresponding time in the past (). must be a non-negative expression and can be estimated. If is negative, it is treated as zero, since future values cannot be known.
Delay statements assume an initial value of zero and work by keeping a table of past values of the expression captured at times when the ODE solver was “on trajectory”
(which includes change points like doses) and by using linear interpolation into that table.
If you’re interested in delay modeling, please look at the Shuhua Hu’s presentation
But still Im not able to write the code in PML as Im facing the problem of incorporating the biexponential equation in the tumor compartment. I need help to write it down and it will be a great help for me.
