New issue

Have a question about this project? Sign up for a free GitHub account to open an issue and contact its maintainers and the community.

By clicking “Sign up for GitHub”, you agree to our terms of service and privacy statement. We’ll occasionally send you account related emails.

Already on GitHub? Sign in to your account

Buccal administration #240

Open
nmens opened this Issue Oct 19, 2018 · 9 comments

Comments

Projects
None yet
2 participants
@nmens

nmens commented Oct 19, 2018

Dear all
Does anyone has experienced to model (on MOBI) buccal administration of a drug?
PK-Sim does not have Buccal administration as an option in the administration protocol, so I need to go for MOBI. The idea is to surpass GI absorption, i.e. the drug is pretended to be completely absorbed into the bloodstream directly from buccal mucosa, avoiding first pass effect.

Many thanks in advance

@msevestre

This comment has been minimized.

Member

msevestre commented Oct 19, 2018

@nmens Can't use a user defined application in PK-Sim for that? (you can specify target organ and compartment as well as a zero order or first order rate)

@msevestre msevestre added the question label Oct 19, 2018

@nmens

This comment has been minimized.

nmens commented Oct 19, 2018

@msevestre thanks for your fast reply!
I tried to follow your suggestion in a common project I have, selecting a User Defined in Administration Protocol, target organ as Venous Blood and Plasma Compartment. I suppose your suggestion for zero order or first order rate is to be selected from Formulation tab. OK.
However, how do I input a buccal permeability parameter? Just using the first order rate (as ka) from the formulation?

@msevestre

This comment has been minimized.

Member

msevestre commented Oct 19, 2018

However, how do I input a buccal permeability parameter? Just using the first order rate (as ka) from the formulation?

This is not available. You have to define your rate to mimic a permeation process. If this does not work, or if you need more control over the process, going to MoBi is the only other alternative

@nmens

This comment has been minimized.

nmens commented Oct 19, 2018

Your initial approach seems simple and nice, avoiding the complexity of MOBI and changes in the spacial structure. Nevertheless, in the case of using only PK-Sim, is it possible to model a partial absorption in the buccal mucosa and the rest thought GI absorption, which may be a possibility in a real world administration by the swallow of the saliva solution.
How would I model this situation? Including two administrations (oral + user defined) at the same time (dose would be fractionated)?

@msevestre

This comment has been minimized.

Member

msevestre commented Oct 19, 2018

@nmens You can use advanced protocols to administer two administrations. However you cannot use UserDefined combined with advanced protocols in that case... Since you are using user defined in VenousBlood Plasma, you could in fact use a normal IV administration instead of UserDefined

@nmens

This comment has been minimized.

nmens commented Oct 20, 2018

@msevestre Thank you very much for your input. So it is possible to use a first order formulation with an IV administration?

@msevestre

This comment has been minimized.

Member

msevestre commented Oct 20, 2018

No it's not (at least not in PKSim out of the box)

In advanced protocol, you can combine IV and Oral as much as you want but you cannot use user defined application.

In simple protocol, you can use user defined application (with first order formulation). However you cannot combine it with another application type such as oral

@nmens

This comment has been minimized.

nmens commented Oct 20, 2018

OK. Once again, I wish to thanks for these precious inputs. I'll follow your advice.

@msevestre

This comment has been minimized.

Member

msevestre commented Oct 20, 2018

Ok no problem. Let us know if you need any help

Sign up for free to join this conversation on GitHub. Already have an account? Sign in to comment