Simulating loading dose IV and then SC afterwards

Hi folks, Question: I want to confirm I’m setting up the simulation input template properly. If I want to simulate an IV loading dose followed by daily SubQ do I set up two columns for each of the routes of administration and say at time =0, AMT in IV route = Dose and then at 24 hrs, 48, hrs, 72 hours etc…include a Dose in SC columns? Thats the first part… do I have to include 2 dosepoint statements in the custom model? One for each route? Thanks Elliot

Hi Eliot, it sounds like you’re on the right track. In fact if you go to the NLME examples guide, Chapter 9, is an example of building this exact type of model using the graphical model builder tool. I would suggest looking at that to confirm your understanding. Simon

Hi Simon, yes that is what I did and seemed to work ok… I also used the ADDL function and added 28 days of repeat SC dosing by mapping a number of additional doses and a delta time to obtain a picture of the whole month of dosing (long half-life so important to get a longer view of the time profile). Works nicely.

Ok, next question,

Background info: I’ve coded a PBPK in PML and I want to be able to change the volume of the SC injection based on the dose being administered in the ADDL. Currently I have it fixed, but I’m not sure how best ot code this in PML when there is a fixed concentration.

So lets say my concentration is always fixed at 100 mg/mL.
Some doses. I want 7 doses at 100 mg (1 mL) and then 7 doses at 30 mg (0.3 mL).
its a depot injection so the volume of the space the drug distributes is dependent partially on the volume being injected.

If I coded the volume as the amount in the dose point, then that amount changes over time and will eventually go to zero…I’m not sure I want that to happen because I have set it up in my model as a standalone anatomical compartment. On the otherhand, maybe its the way to go if the remainder of the anatomical compartment grows as the depot portion shrinks…

nonetheles what is your opinion as the best way to code the initial volume going in if you have a single dose point, and ADDL where the dose changes and consequently the volume being injected changes?
thanks
elliot

Hi Elliot. Not sure I understand well the question. Do you have the code you generated and if so what is the variable you want to change dynamically to keep the concentration constant. Do you mean the input dose in terms of concentration constant.