# How to code fraction excreted for sequential metabolism model

**URL:** <https://forum.certara.com/t/how-to-code-fraction-excreted-for-sequential-metabolism-model/3663>\
**Category:** PML School\
**Created:** [February 20, 2023, 6:28pm UTC](https://forum.certara.com/t/how-to-code-fraction-excreted-for-sequential-metabolism-model/3663 "2023-02-20T18:28:57Z")\
**Posts on this page:** 3\
**Page:** 1

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**Author:** ![tienle](https://avatars.discourse-cdn.com/v4/letter/t/e274bd/32.png) [@tienle](https://forum.certara.com/u/tienle)\
**Post date:** [February 20, 2023, 6:28pm UTC](https://forum.certara.com/t/how-to-code-fraction-excreted-for-sequential-metabolism-model/3663/1 "2023-02-20T18:28:57Z")

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Good afternoon,

I am trying to build a PopPk model for a drug with its metabolite as a sequential model (parent drug → metabolite 1 → metabolite 2).

I am trying to model the fraction excreted in urine compartment and fraction metabolized, and want to specify in the model that fe + fm = 1. I do not know how to code that in the textual model. Can I please get help with this issue?

Another issue, when I was trying to model simultaneous plasma and urine data, my final estimates for fe parameters were not estimated by the model. I kept getting an error message saying:

“Fixed effect ‘tvFe’ is not used and will be frozen  
Random effect ‘nFe’ is not used  
Structural parameter ‘Fe’ is not used”  
Could anyone please explain what went wrong here? Thank you!

I attached the picture of the graphical model I built below. Thank you so much and I greatly appreciate any help!

C: parent drug  
C2: metabolite 1  
C3: metabolite 2  
A0: urine data for parent drug  
A4: urine data for metabolite 1  
A5: urine data for metabolite 2  
Q\_C\_C2: formation clearance (parent drug to metabolite 1)  
Q\_C2\_C3: formation clearance (metabolite 1 to metabolite 2)  
Cl: renal clearance of parent drug  
Cl\_C2\_A4: renal clearance of metabolite 1  
Cl\_C3\_A5: renal clearance of metabolite 2

 ![Screenshot_20230206_063905.png](https://us1.discourse-cdn.com/certara/original/1X/5fb2ad0de84c27bc45fcce6df7e5c5d077fd335a.png)

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**Author:** ![cradhakr](https://avatars.discourse-cdn.com/v4/letter/c/7feea3/32.png) [@cradhakr](https://forum.certara.com/u/cradhakr)\
**Post date:** [February 20, 2023, 10:53pm UTC](https://forum.certara.com/t/how-to-code-fraction-excreted-for-sequential-metabolism-model/3663/2 "2023-02-20T22:53:26Z")

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Hi,

I have attached an link to PML School conducted by Certara - this could be of use to you to model parent and metabolite.

[https://support.certara.com/forums/topic/928-lesson-2-parent-and-metabolite-kinetics/](https://support.certara.com/forums/topic/928-lesson-2-parent-and-metabolite-kinetics/)

To address your specific question on tvFe, is it possible for you to share the project file for us to investigate further? If you would like to keep it confidential please e-mail to [support@certara.com](mailto:support@certara.com)

Thanks & Regards

Mouli

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**Author:** ![tienle](https://avatars.discourse-cdn.com/v4/letter/t/e274bd/32.png) [@tienle](https://forum.certara.com/u/tienle)\
**Post date:** [February 21, 2023, 3:46pm UTC](https://forum.certara.com/t/how-to-code-fraction-excreted-for-sequential-metabolism-model/3663/3 "2023-02-21T15:46:26Z")

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> [@cradhakr](#):
>
> Hi,
> 
> I have attached an link to PML School conducted by Certara - this could be of use to you to model parent and metabolite.
> 
> [https://support.certara.com/forums/topic/928-lesson-2-parent-and-metabolite-kinetics/](https://support.certara.com/forums/topic/928-lesson-2-parent-and-metabolite-kinetics/)
> 
> To address your specific question on tvFe, is it possible for you to share the project file for us to investigate further? If you would like to keep it confidential please e-mail to [support@certara.com](mailto:support@certara.com)
> 
> Thanks & Regards
> 
> Mouli

Hi Mouli,

Thank you for sending the lecture note for parent and metabolite modeling. I appreciate it!

I am happy to share the project. I will email it to [support@certara.com](mailto:support@certara.com) shortly.

Thank you,

Tien
