Finite dose

[MelanieMartha26]

Dear everyone,

I was wondering whether it was possible to insert an event with a finite dose for the skin permeation model, and if so, how this can be achieved. Thank you very much in advance!!

Best regards,

Mèlanie

[abdullahhamadeh]

Hello Mèlanie,

You may set one or more dosing events in the Events building block of arbitrary size and start time, as described in section 4.2 of the user guide:

You can also set the volatility of the vehicle to model the four dosing scenarios in Dancik et al, 2013 (cases I-IV) using the "Volatile vehicle" and "Vehicle type" inputs in the favorites menu. eg to model cases I/II you need to set Volatile vehicle = 1 or Vehicle type = 0 (where 0 corresponds to a neat application of the permeant to skin).

Hope this helps, and please let me know if any clarification is needed.

[MelanieMartha26]

Dear @abdullahhamadeh thank you very much for your swift response. I do understand how to change an event; however, it is not yet completely clear to me how one can remove the permeant that is still left on the skin after several hours. For example, I would like to simulate what happens when you apply a dose and then after 8 hours "clean" the skin. I want to simulate the model for more than 8 hours as I am curious what the end systemic exposure will be.

I hope this is clear to you, otherwise please don't hesitate to tell me.

Best regards,

Mèlanie

[abdullahhamadeh]

Hi @MelanieMartha26

Every time a dose is "added" it is assumed that any dose that was previously on the skin surface is removed. So what you need here can be accomplished by simply adding another event_with_dose_mass_entered_manually event group where the dose is zero.

Step 1: First, save event_with_dose_mass_entered_manually as a PKML file. Then delete event_with_dose_mass_from_spatial_structure.

Step 2: Rename event_with_dose_mass_entered_manually to dose_addition.

Step 3: Right-click on skin_application and select Load Event Group... and select the previously saved PKML file containing event_with_dose_mass_entered_manually.

Step 4: Rename the newly-added Event Group to dose_removal.

Step 5: Set the start times and doses for the dose addition and dose removal. For example, under dose_addition, you can add a 10 ug/sq cm dose at time = 0 hours by setting Dose_time = 0 h and Mass_dose_per_area = 10 µg/cm². Under dose_removal, you can remove the previously-added dose at 12 hours by setting Dose_time = 12 h and Mass_dose_per_area = 0 µg/cm².

Step 6: You can verify the addition and removal works by simulation the model with this new event structure and plotting the results of the Vehicle mass per area observer, which shows the removal of the dose at 12 hours:

[MelanieMartha26]

Dear @abdullahhamadeh

Thank you very much! I tried this earlier, but somehow I made some mistakes, now I get it, thank you!