Question about Drug Dissolution in Generic Simbiology PBPK

Hello,

I have a question about drug dissolution in Generic SimBiology PBPK model Version 1.2.1.1. Upon refering to the units for drug undissolved and drug dissolved, they are defined as mg and mg/mL, respectively in the PBPK model. However, I am not clear on how the drug dissolved units changed to concentration without considering the volume of the compartment. The original sheila peters papers seems to consider drug dissolved also to be in the units of amount (mg). Could someone please let me know if I am missing something here or would you rather think the equation for gut dissolution (for example in duodenum) to be changed from kDissolution * Duodenum.DrugSolid * (DuodenumSolubility - Duodenum.DrugDissolved) to kDissolution * Duodenum.DrugSolid * (DuodenumSolubility - Duodenum.DrugDissolved/ Duodenum) (considering the correct units for Duodenum.DrugDissolved is in amount as per original paper) ?

Thank you very much!

Answer 1

[Ayush]

Hello Bhargavi,

Your main concern with the Generic SimBiology PBPK model version 1.2.1.1 is about the difference between the units for drug undissolved (mg) and drug dissolved (mg/mL). I went through the paper referenced in the creation of this model and it does have the units of drug dissolved in amount(mg) and not concentration(mg/mL), hence validating your problem.

Based on the community discussion on the Generic SimBiology PBPK Model, it can be observed that the file exchange model will detect the dimensions of the reactions before simulation and the volume of the compartment will be multiplied accordingly with the formula to balance the consideration of concentration dimensions similar to your case. Please refer to the below link for the community discussion for more details as it might be suitable and valid for your problem as well:

https://www.mathworks.com/matlabcentral/fileexchange/37752-generic-simbiology-pbpk-model?tab=discussions#discussions_2547236

Hope it helps!

[Bhargavi Srija Ramisetty]

Thank you for the reply, Ayush.