Unexpected linkage of renal elimination processes to multiple metabolites after pregnancy model customization

[Seoyeonchoe]

Hello,

I am currently developing a pregnancy PBPK model by extending the model structure in MoBi and subsequently importing the model into PK-Sim for simulation.

After extending the pregnancy-specific compartments and running simulations in PK-Sim, I observed that the predicted concentrations were substantially lower than expected. While investigating the source of this underprediction, I reviewed the model structure in MoBi and identified what appears to be an unusual linkage pattern for renal elimination processes.

Specifically, I found that glomerular filtration and renal clearance processes are connected not only to their intended compound/metabolite, but also to multiple other molecules (parent compound and metabolites).

I expected that each compound or metabolite would be associated with its own renal elimination process. However, in this model, the same elimination process appears to be linked to several molecules simultaneously.

As shown in the attached figure, I observed structures similar to:

BUP renal clearance → BUP, TBUP, EBUP
TBUP renal clearance → BUP, TBUP, EBUP
EBUP renal clearance → BUP, TBUP, EBUP

Additionally, this linkage pattern was not observed in the original non-pregnant model. The issue was identified during the review of the customized pregnancy model after extending the pregnancy-specific structure.

Therefore, I would greatly appreciate any guidance regarding whether this structure is expected or whether it may indicate a model configuration issue.

Thank you very much.

[github-actions[bot]]

🤖 Discussion Assistant: I found some similar discussions that might be helpful:

• Pregnancy model no renal clearance (78% similar)
• Pregnancy Model include renal clearance for metabolites (76% similar)
• Setting up a coupled Parent-Metabolite PBPK model (73% similar)
• MoBi 11.2: Cannot create simulation with Pregnant Woman spatial structure for rifampicin (73% similar)
• How does the pregnant population work in PK-Sim? (72% similar) ✅ (Answered)