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Parent drug with metabolites and GI pre-systemic metabolism


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#1 Davidq8

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Posted 23 October 2022 - 12:24 AM

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Hi
I am trying to build a PopPk model for a drug with its metabolite (active) as a joint model. I found a published model where they modeled the portion of the metabolite formed from the parent drug in GI (pre-systemic). I tried to build a similar model using the graphical interface option in NLME.
 
For pre-systemic metabolism, I created a deposit compartment using the (Duration) function in the absorption compartment and then two absorption rates, one to the central compartment of the parent drug and another directly to the central compartment of the metabolite. I am unsure if this defined the pre-systemic metabolism step described in the published model.
 
The other issue, I am trying to model the fraction of parent drug clearance attributed to metabolite formation and the fraction to other not active metabolites (not needed to be included in the model). I do not know how to do that using NLME. 
 
Can I get help with this issue?
 
I attached the model file I created and the pharmacokinetic model structure for the published paper. 

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#2 htran

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Posted 08 September 2023 - 02:27 PM

I am trying to generate a similar model as well - with oral administration - hypothesis: there is a significant GIT enzymatic conversion to metabolites.

 

David: I noticed that your model - you chose "extravascular" but your agent is given IV. is this correct?



#3 Davidq8

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Posted 19 September 2023 - 09:59 PM

I am trying to generate a similar model as well - with oral administration - hypothesis: there is a significant GIT enzymatic conversion to metabolites.

 

David: I noticed that your model - you chose "extravascular" but your agent is given IV. is this correct?

Hi htran

The drug I am working on is an oral drug






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