Feature: New Total Hepatic Clearance: CLint/#Cells

StephanSchaller commented 4 years ago

There is "In-vitro hepatocytes - t1/2" and "... - residual fraction"...but not "... - intrinsic clearance". We should provide the latter when CLint is measured as µM/min/10^6 cells in hepatocyte assays.

msevestre commented 4 years ago

Relatively low effort if the formula is clear

StephanSchaller commented 4 years ago

OKay, we will make a proposition

StephanSchaller commented 4 years ago

We could actually have two processes: (A possible reference for the calculation is: Bonn et al 2016)

Name: In-vitro hepatocytes - CLint (Volume)

Variables in Formula (similar to other in.vitro processes):

Number of cells/g liver tissue (N_liv)
Fraction intracellular (Liver) (f_cell)
Fraction unbound in incubation (fu_mic)
Tissue Densitiy (actually is missing in the other formulas? otherwise the dimension does not add up to 1/min but remains ml/(g*min), not a big issue as it is 1 anyway) (d)
in-vitro CLint (in [µl/min/10^6 cells]) (CLint)

--> Specific CL = CLint*N_liv/fu_mic/f_cell*d

Name: In-vitro hepatocytes - CLint (Mass)

Variables in Formula (similar to other in.vitro processes):

Number of cells/g liver tissue (N_liv)
Fraction intracellular (Liver) (f_cell)
Fraction unbound in incubation (fu_mic)
Tissue Densitiy (actually is missing in the other formulas? otherwise the dimension does not add up to 1/min but remains ml/(g*min), not a big issue as it is 1 anyway) (d)
in-vitro CLint (in [µM/min/10^6 cells]) (CLint)
Total concentration of drug in incubation (C_drug)

--> Specific CL = CLint/C_drug*N_liv/fu_mic/f_cell*d

StephanSchaller commented 3 years ago

@abdelr , do we get this for V10?

msevestre commented 3 years ago

Nope

StephanSchaller commented 3 years ago

Not a chance to slip it in? :-D

msevestre commented 3 years ago

Not for v10. It requires changes in the DB. It will potentially impact order of processes etc...we are done with all tests. Let's schedule this for next update

StephanSchaller commented 2 years ago

We should add "microlitre/ml/million cells" as a dimension, see https://github.com/Open-Systems-Pharmacology/Forum/discussions/1251

StephanSchaller commented 1 year ago

@Yuri05, @PavelBal, @msevestre, @rwmcintosh can we include this in the next update?

msevestre commented 1 year ago

@StephanSchaller @PavelBal Thsi is not complete .We are missing a description here is what we have for the two process so far

In vitro hepatocytes - t1/2: Total hepatic clearance is described as first order process in the liver, which eliminates the compound from plasma. Specific clearance is calculated using the residual fraction at a given timepoint as input value which was determined in an in vitro hepatocyte assay.
In vitro hepatocytes - residual fraction: Total hepatic clearance is described as first order process in the liver, which eliminates the compound from plasma. Specific clearance is calculated from t1/2 as input value which was determined in an in vitro hepatocyte assay.

msevestre commented 1 year ago

@StephanSchaller @Yuri05 @PavelBal This definition adds two new dimensions that we do not have. That means that we need to update ALL packages for this update Doable, but....in this case I also need the dimension file to be updated. This becomes a lot of work.

@Yuri05 your call.

msevestre commented 1 year ago

This will not be part of this release as the changes are too complex at this stage (and specs are not complete as parameter name and descriptions are missing)

StephanSchaller commented 1 month ago

@Yuri05 , @msevestre , same here, assign us and clarify with @PavelBal in the next Dev Meeting

PavelBal commented 1 month ago

@Yuri05 @msevestre could you review what is missing?

Open-Systems-Pharmacology / PK-Sim

Feature: New Total Hepatic Clearance: CLint/#Cells #1489