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PK-Sim and Specific Clearance #176

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krinaj opened this Issue May 11, 2018 · 4 comments

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krinaj commented May 11, 2018

Hello,

I am trying to understand how biliary elimination processes should be added in PK-Sim if data comes from in vitro studies to put together some IVIVE workflows in #101 . And I want to confirm that I am understanding this correctly.

Let's say I am using data from a paper and description is as follows:
image

Now, I have from results is PSbile and fu(experiment), and PSbile is actually PSbile_app/fu (as described above). To add this in PK-Sim --> biliary clearance --> Plasma Clearance, I need to add apparent biliary clearance (which will be PSbile*fu) since plasma clearance will be scaled within PK-Sim to get specific clearance by considering protein binding and volume of compartment. Is that understanding correct or am I confused about specific clearance?

Thanks,
Krian

@msevestre msevestre added the question label May 15, 2018

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StephanSchaller commented May 16, 2018

@msevestre , can we get an IVIVE label we can add to questions?

@msevestre msevestre added the IVIVE label May 16, 2018

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msevestre commented May 16, 2018

done

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StephanSchaller commented May 16, 2018

@krinaj , that's indeed an interesting paper you have there! Could be interesting to revisit IVIVE results for the listed compounds...!

Regarding your approach I have some doubts, as:

  • PK-Sim requires a value for plasma (not intrinsic) clearance (normalized to body weight)
  • The fu(hep) from your paper is not the same as the fu (plasma) from PK-Sim, but the intracellular fraction unbound in hepatocytes. In PK-Sim, this corresponds to the "Partition coefficient (Water/Cell)" which is only visible in MoBi...

So I think we need a new biliary clearance "process type" from in-vitro to account for sandwich cultured hepatocytes...

If I am not mistaken, with your data you may now multiply the intrinsic PSbile with the average human hepatocyte volume (average rat hepatocyte volume in your paper was given as 5.2 μL/mg protein) and use this then directly as specific clearance value... (ignoring the above entries in PK-Sim)...?

@Yuri05 , any other experiences here with in-vitro data for biliary clearance?

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krinaj commented May 17, 2018

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