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Open-Systems-Pharmacology / Pregnancy-Models

Physiologically Based Pharmacokinetic Models for Pregnant Women
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Extending a pregnant model with fetal subcompartments #19

Closed EAalgh closed 2 years ago

EAalgh commented 3 years ago

Hi there, I followed the tutorial of Dallman et al to add new compartments (here is fetal brain ) to an existing pregnant model in MoBi. I managed ti intorduce Fetal Brain and make all wiring to circulation. At the step of defining the partition coefficient Interstital/Water (step #5 in the suppl. information tutorial), I can find "PARAM_K_Water_INT_FetalBrain" on the drop-down menu option, only "PARAM_K_Water_INT_Fetus". I wonder if something is missing in the Spatial structure that I made. Compartemnt FetalBrain is connected to neiborhood ArterialBlood_UmbilicalCord and VenousBlood_Umbilical Cord. The MoBi file is attached. Thanks in advance! Pregnant_fetal Brain_extension_2.zip

AndreDlm commented 3 years ago

Hi @EAalgh,

thanks for sharing your model. Looking at your model, I can confirm that you have a Partition coefficient (interstitial/water) implemented in the neighborhood of FetalBrain_int_FetalBrain_Cell. However, the potential issue is that this Partition coefficient (interstitial/water) uses the formula that has been defined for the Fetus compartment, i.e. the value of the partition coefficient in the FetalBrain compartment will always be the same as in the Fetus compartment.

Note, that the Partition coefficient (interstitial/water) is calculated from fraction unbound (fu) and the Partition coefficient (interstitial/plasma) as follows: image

And the Partition coefficient (interstitial/plasma) is calculated as follows: image

Hence, if you assume that all variables in this equation have the same value in the Fetus compartment and the FetalBrain compartment, then you don't need to change anything. You can find more information on the equation above here.

If you want different drug partitioning between interstitial and water compartments in the FetalBrain and Fetus, then you need to define a new equation for the Partition coefficient (interstitial/water) in the neighborhood of the FetalBrain as described in step 5) of the tutorial.

I hope this helps!

André

EAalgh commented 2 years ago

Hello again, Thanks for the help. I now have a pregnant model extended to inlcude 2 fetal subcompartments. The last step should be to create a simulation using the new spatial sturcture and then export it to pKsim. When I try to create a simulation I get an error message. https://user-images.githubusercontent.com/84385506/135580301-d1e78e71-59c9-4c34-8547-a79f51bcbdd7.png If I save the already existing simulation that I have in MoBi before extending to the fetal subcompartment as pkml file and try to import it to pksim, I get another error message. https://user-images.githubusercontent.com/84385506/135580541-db9d6757-9b52-4c26-bb36-36e764cfa959.png What I did is that i extended my model which was created in pregnant woman (attached pkml: trialpregsim) to inlcude fetal sub compartments in Mobi (Pregnant fetal brain extension k values).

I attach the respective files for reference.

pregnant fetal_Brain extension_3.zip

Thanks in advance!

AndreDlm commented 2 years ago

Hello @EAalgh, has this issue been solved in the meantime or do you still need help?

AndreDlm commented 2 years ago

Dear @EAalgh, I will close this issue. Please re-open if the issue still persists. Thanks