Skip to content
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

A question on formulas and in distribution model #398

Open
wangwei1619 opened this issue Oct 14, 2019 · 4 comments
Labels

Comments

@wangwei1619
Copy link

@wangwei1619 wangwei1619 commented Oct 14, 2019

Hi, all,

When I learn the formula in MoBi, I find this passive transport PassiveDiffusionPl2Int is defined as "dN/dt=fu * P_endothelial * SA * (C_pls - C_int / K_int_pls)"; isn't the term "C_pls - C_int / K_int_pls" is equal to 0?
image

@HenrikCordes

This comment has been minimized.

Copy link

@HenrikCordes HenrikCordes commented Oct 15, 2019

Dear @wangwei1619,

passive diffusion will only take place, if there is a difference in unbound concentration between the two spaces (plasma and interstitial).
In MoBI you can select "create process rate parameter" and "plot parameter" to have a look at the PassiveDiffusionPl2Int in one of your simulations. You will find that PassiveDiffusionPl2Int is basically never 0 (except for the turning point or when there is no drug in the system any more).

On the other hand, if you set all clearane parameter (hepatic, enzymatic & renal) in your PBPK model to 0 and simulate your system for a long time periode (1000 h or more) you will find that at some point PassiveDiffusionPl2Int will become 0. This is when the system is in equilibrium and the unbound concentration in bothe spaces (here, plasma and interstitial) are equal.

Hope this helps!

Kind regards,
Henrik

@wangwei1619

This comment has been minimized.

Copy link
Author

@wangwei1619 wangwei1619 commented Oct 15, 2019

Dear Henrik,

Thanks for your advice. But I don't know how to create process rate parameter and to plot it. When I right-clicked on the simulation, I didn't find "create process rate parameter" .
image
Now, I get your idea that unbound concentration between the two spaces (plasma and interstitial) are not equal during equilibrium process, but, another problem comes. I thought Cu + Cb = Ctotal in a compart because V *(Cu + Cb)= V * Ctotal. However, as the PK-Sim takes account protein as another compart, I think unbound and bound drug don't share the same distribution volume, is it right? And, basing on this change, what is the relationship among Cu, Cb, C_water, C_protein, Vf(water/plasma) and Vf(protein/plasma)?

Best regards,
Wang Wei

@HenrikCordes

This comment has been minimized.

Copy link

@HenrikCordes HenrikCordes commented Oct 15, 2019

Dear @wangwei1619,

in MoBi you have to open the "passive transport" building block:
image
and than go to PassiveDiffusionInt2Cell and check the boxes:
image

Kind regards,
Henrik

@wangwei1619

This comment has been minimized.

Copy link
Author

@wangwei1619 wangwei1619 commented Oct 16, 2019

Hi, Henrik,
Thanks for your help, I got it. But I am still confusing with these parameters Cu, Cb, C_water, C_protein, Vf(water) and Vf(protein). According to the calculation method of PK-Sim standard method:
image
it can deduce that C_plsfu=Cu=C_water=NuV_water_pls, which means fu here is equal to (NuV_pls)/(N_plsV_water_pls). It is not identical to what is generally used that fu=Cu/(Cu+Cb)=Nu/(Nu+Nb)=Nu/N_pls. On the other hand, Cu could be assumed to equal C_water, because plasma almost consists of water.

Sign up for free to join this conversation on GitHub. Already have an account? Sign in to comment
Projects
None yet
3 participants
You can’t perform that action at this time.