I don't know the original mathematical model but based on the project you shared, I can recommend the following:
- I recommend you to activate Unit Conversion in the Simulation settings since you use different time units in the model and smiulation program (minute vs second).
- There seems to be an issue with the ODE driving the concentration of IL-23. The term ParacrineConsumption is currently independent of free drug:
which seems in contradiction with the events.
I assume you didn't set 
to 0 at t=0 since it would be 
with the current implementation.
to 0 at t=0 since it would be with the current implementation. Having ParacrineConsumption being a constant and thus independent of IL-23 can indeed lead to negative values.
3. Once the points above are solved, you could use a scheduled dose instead of multiple events to modify the value of . Schedule doses provide a way to specific each dosing time and dosing amount separately in a schedule table. You can create a schedule dose by clicking in the Type column of the table of doses.
. Schedule doses provide a way to specific each dosing time and dosing amount separately in a schedule table. You can create a schedule dose by clicking in the Type column of the table of doses.
Using a schedule dose is more efficient than events if the triggers occur at a predefined list of timepoints.
By the way, not artificially constraining IL-23 to always be positive makes it possible to see the issue described in point 2.
I hope this helps.
Best regards,
Jérémy
