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Reference for in vitro hepatocytes T/2 #402

Closed teutonicod closed 5 years ago

teutonicod commented 5 years ago

Dear all,

I am trying to use the IVIVE option in PK-Sim which allows you to input the T/2 in hepatocytes and calculate the intrinsic clearance. Is there a reference for the equation used (see screenshot below)? In this equation there is the fraction unbound in the essay, which in this case would be Fu_Hep and I am having problems to understand why increasing the Fu_Hep for the same T/2 we see a decrease in the clearance. (Since from my point of view: higher Fu_Hep= more drug available in the essay, so for the same T/2 this would mean higher clearance...) Any help is highly appreciated! Thanks, Donato

image

tobiasK2001 commented 5 years ago

Dear Donato,

I am not sure if this is the direct reference, but some basic equations and concepts you will find here: https://www.ncbi.nlm.nih.gov/pubmed/9336307 e.g. Equation 11 might be usefull image

From that it appears logical that increasing fu_Hep will result in a lower Clint, if t1/2 is kept constant as it is together with the t1/2 in the denominator.

Hope this might help you.

Best, Tobias

teutonicod commented 5 years ago

Hi @tobiasK2001 , Thank you very much! It is exactly what I was looking for to better understand this point! Donato

teutonicod commented 5 years ago

Hi @msevestre, would it be possible to add this reference to the software? Like in the value origin? Since also other users can have the question about the origin of this equation.

Donato

msevestre commented 5 years ago

@teutonicod Can you please create an issue in the PKSim repo?