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Enterohepatic Recycling - clearance problem

Clearance negative

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#1 Xiuqing Gao

Xiuqing Gao

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Posted 19 December 2019 - 09:39 PM

Hi Everyone

 

I am working on a small molecule with enterohepatic recycling on pharmacokientic study after extravascular administration. However, the model fitting and CV% seems good for pharmacokinetic parameters except clearance for central compartment (always gave the negative values)!! 

 

I have also tried transition model, but all of the model i tried always gave me the negative value for central compartment clearance value (graph fitting and CV% always are great). 

 

Does anyone can explain this issue?

 

Please check my models and results, I am looking forward to your response!!! Thank you!!!!

 

 

 

Best regards,

Xiuqing Gao

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Edited by Xiuqing Gao, 19 December 2019 - 09:41 PM.

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#2 bwendt@certara.com

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Posted 20 December 2019 - 12:07 PM

Dear Xiuqing,

 

your data does not capture absorption, for most of your profiles the first time point represents Tmax, for some profiles the second time point represents Tmax. So you would be better off using IV bolus or IV infusion rather than extravascular dosing. But EHC model is not the right one. Try with a more simple model, e.g. dual absorption mode. We had a webinar on that topic a while ago:

 

https://support.cert...-model-builder/

 

 

Bernd



#3 Xiuqing Gao

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Posted 25 December 2019 - 11:07 PM

Dear Bernd

 

Yeah, the absorption is pretty fast for some reason. And I saw the multiple absorption model online. Since it is oral administration data, i am not sure if i can use multiple absorption in this case. I will try with some simple model to fitting them.

 

Thank you for your help!

 

Xiuqing Gao

Dear Xiuqing,

 

your data does not capture absorption, for most of your profiles the first time point represents Tmax, for some profiles the second time point represents Tmax. So you would be better off using IV bolus or IV infusion rather than extravascular dosing. But EHC model is not the right one. Try with a more simple model, e.g. dual absorption mode. We had a webinar on that topic a while ago:

 

https://support.cert...-model-builder/

 

 

Bernd






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