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IVIVE total hepatic clearance definitions #306

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PriKalra opened this Issue Apr 9, 2019 · 0 comments

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PriKalra commented Apr 9, 2019

Dear All,

I have read through the OSPSuite definitions and the stimulating discussions in the threads #125, #176 and #177. However, I would like to have insights on the situation I have w.r.t. the available data and a reconfirmation as to my implementation is correct or needs reconsideration.

In my case, for the compounds, we do not have the knowledge on the metabolizing enzymes. The only data that I have w.r.t. metabolism is total clearance (one of the either, depending on the compound) via:
S9 : intrinsic clearance in S9 subfraction (µl/min/mg protein)
Microsomes: intrinsic clearance microsome subcellular fraction (µl/min/mg protein)
Hepatocytes: µl/min/10^6 cells

Moreover, in any of the cases, I do not have information on the t1/2 of the assay or measuring time.

  1. Therefore, in such a situation, how do I differentiate as to which process type should I use among the highlighted?
    So far, I have used residual fraction to define the clearances
    ( In vitro hepatocyte residual fraction for Hepatocytes
    and In vitro liver microsomes residual fraction for Microsomes and S9 subfractions) where I have calculated the value of Specific clearance from the data. Am I taking the correct approach? Should I be vary of anything else?

image

Example for hepatocytes where i converted the clearance to compute specific clearance (µl/min/10^6 cells*hepatocellularity number * liver density= 1/min ):
image

Thanks and best,
Priyata

@msevestre msevestre added the question label Apr 17, 2019

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