Variability of MoBi parameter

[ccastellano1-lgtm]

Hello everyone,

I am working with a TMDD model built in MoBi and then exported to PK-Sim for population simulations. The model includes a monoclonal antibody, a target receptor, a complex, FcRn-related recycling, and target-mediated internalization.

I was able to perform the parameter estimation in MoBi and obtained a reasonable global fit. I would now like to introduce interindividual variability in some MoBi-defined parameters when running a PK-Sim population simulation with 250 virtual mice.

The parameters I would like to vary are mainly:

Target, representing interindividual variability in baseline target amount.
kint, representing variability in target-mediated internalization.

The initial amount of Target in the model is currently defined in the Initial Conditions building block as:

Target | Organism | VenousBlood | Plasma | 7.38E-5 µmol

When I export the model to PK-Sim and create a population simulation, the User Defined Variability section only shows standard PK-Sim parameters, such as compound properties, organ volumes, physiology, permeability, etc. My MoBi-defined parameters such as Target or kint do not appear there as parameters that can be varied in the population.

My questions are:

What is the recommended way to expose MoBi-defined local parameters so that they appear in PK-Sim under User Defined Variability?
Is it possible to apply population variability directly to an Initial Condition, such as the initial amount of Target in VenousBlood/Plasma?
If Initial Conditions cannot be parameterized directly, is the recommended approach to use an event at time zero to set the target amount as Target_ref * Target_factor?
If this is not possible through the PK-Sim interface, is the recommended workflow to use OSPSuite-R and modify the target amount or kint values individual by individual?

The goal is to generate a population simulation where the baseline target amount varies between individuals, for example using a log-normal distribution around the reference value, while keeping the core binding parameters fixed.

Any guidance on the correct OSP workflow for this would be very helpful.

Thank you.

[github-actions[bot]]

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[Yuri05]

Before exporting a simulation to PK-Sim make sure to mark your parameters of interest as variable (in populations) in MoBi
(in their corresponding building blocks, then update the simulation from building blocks)