build a pk model with dual release having different lagtimes

Phoenix Certara Forums Modelling and Simulation
1

Hi,

Can someone show me how to create a model in Phoenix for a drug product with dual release (50% IR and 50% ER) and have a lagtime for each component? I tried adding a 2nd lagtime to the graphical model but I was not successful.

The dose is 1300 mg and concentration is in ug/mL. Attach is the project file (Phx 8.0) with the dataset.

Thanks

John

dual release.phxproj (43.2 KB)

2

I think I have seen something similar to this with an inhalation model, althoguh the one I found on the forum is not the one i was thinking of, as they had to model the splitting of the dose between the drug that was absorbed by lungs versus orally.

https://support.certara.com/forums/topic/1076-inhalation-model/

In your case, I think it is easier, since you know that the dose form is 50/50 so I would just put two dose points on the model, (edit it in Graphical mode)

You could make ER have a tlag, or perhaps zero order, although I think you may have some identifiability issues.

Simon.

ER_Ir_tlag.jpg
ER_Ir_tlag.jpg1200×754 72.4 KB
ER_IRabs.phxproj (137 KB)

3

Thank you Simon. I will give it a try.

John

4

Hi Simon,

Were you referring to this posting?

https://support.certara.com/forums/topic/467-models-for-simultaneous-1-0-order-absorption/

Many thanks.

John

5

actually, it was a different problem - maybe it was a support case and not a forum thread!

that is also a nice one to look at though.

Simon.

6

Thanks Simon. I played around with the fit and so far it’s promising…

John

ER 1300.phxproj (563 KB)

7

Hi Simon,

Question, what if I dont know the dose? The issue i have is that my drug is dual release with IR - ER. There is a possibility that the ER component also has two release. It’s a matrix gel release formulation and upon exposing to water a small portion (don’t know how much) could be released immediately. Rest of the drug would come out of the gel layer later on at a slower rate eventually.. With this I dont know how much of the ER is coming out initially (at a faster rate) follow by the remaining amount coming out at a slower rate.

Thanks

John

8

You can model the fraction of dose - I’d have to search to see if I can find an example of the code, but I am sure it was using the split dosepoint option and modelling that fraction. of course you may well have an identifiability issue as you may be making the model more complicated than the data can support. I’m up against a project deadline at the moment but will try to come back to this if someone else hasn’t been able to help you.

in the mean time I’d try reading the NLME user guide and the PML modeling language manual at split and bioavailability

Please let us know how you get on, and if you can post an example you need double checking or assistance on that would help too.
Simon.