Adding two different dose regimes to achieve full dose scheme

Hello,

I'm looking to simulate the PK profile of a molecule. The dosing scheme I'm looking to simulate is the following: 20 mcg on Day 1, 30 mcg on Day 8, 68 mcg on Day 15, and 68 mcg once every week thereafter. To implement this, I added two dosing regimes to the model, one scheduled dose regime that included the first three doses, and another repeat dose regime to include the weekly 68 mcg applied starting from the 22nd. I then assumed that in the simulation, if I activated both dose regimes, I'd get the full dosing scheme I'm looking for. Unfortunately that doesn't seem to be the case, only the repeat dose schedule is shown. Can someone help me figure out what I'm doing wrong? I can upload my model file if need be. Many thanks in advance!

[Arthur Goldsipe]

Yes, please share the file and instructions on how to reproduce the problem. I'm not sure how to identify the issue without that.

[mitpi_182]

Yes, sorry should've attached it from the start. The file is a simple two-compartment model with the two dosing schemes described above. If you go to the model analyzer, I think I've activated both dosing schemes but the PK profiles only reflect the repeated dose scheme when I run the model.

Answer 1

[Arthur Goldsipe]

I opened the project you attached, and I do see that both doses get applied.

Note that I increased the simulation stop time to allow time for both doses to get applied. One thing to note is that the doses get applied to different species, and those doses have very different units. Dose "Approved Dose Regimen" is applied to species Drug_Peripheral, which has units of milligram/liter. Since your Peripheral compartment volume is 470 liter, the scale of the concentrations is ~10^-3 milligram/liter. Dose "Dose Schedule" is applied to species Dose_Peripheral, which has units of milligram. So the scale of the amounts is ~1 milligram.

You can see a plot of the concentrations in the updated project I'm attaching. I'm also including a copy of the plot below.