krinaj
commented
6 years ago Hello Biju,
I do not think there is a workaround in PK-Sim. You will have to use Mobi. I had similar issues creating a nasal absorption compartment and Pavel's comment to my question (https://github.com/Open-Systems-Pharmacology/MoBi/issues/246) was really helpful. It provides step by step direction.
Hope this helps.
Krina
biju-benjamin
Hi I am trying to incorporate a subcutaneous compartment into a working iv-PBPK model to be used for population simulation. The idea is to use de-convolved cumulative-fraction absorbed profile as input from subcutaneous to plasma assuming no clearance in the subcutaneous compartment
Tried the following with PK-sim created a custom administration profile with skin as the target organ and interstitial space as target compartment. A table formulation was created with cumulative fraction absorbed as table values. Simulation worked As a second step changed the target compartment to plasma and repeated the simulation . Both results look alike visually.
Query -1-2 I doubt if any of the above is the correct approach considering that de-convolution of SC data with iv provides an input function/profile to plasma from the extra-vascular site, and I assume in the above cases the drug released is subject to a built in passive diffusion function inside PK-sim therefore
1) Any comments on a workaround with PK-sim
Tried the following with Mobi
Exported the working iv population simulation as pkml created a spatial structure for subcutaneous (organ, physical), defined neighborhood with venous plasma. Created a global compound parameter"'Sc_abn" with table as formula type , fraction as dimension and input the de-convolution data into table. In the passive transport building block created a new property "SubcutaneousAbsorption with a formula Sc_abn Total drug mass
2) Is the previous formula, the correct thing to do
I am not very sure of the next steps. If I can get some workflow tips, the following is what I need
Query 3-5
3) How do I specify dose for a simulation. Does it need to be defined in events (steps if any appreciated)
4) How to perform population simulations using this model by exporting to PK-sim with administration to subcutaneous compartment.
5) Is there a way to make this newly created 'subcutaneous compartment' appear in the user defined administration protocol after exporting to PKsim.
Thanks in advance
Biju Benjamin