# Problems with AUC calculation and dose simulation when using a steady-state model

AUC calculation Dose simulation Steady state

4 replies to this topic

### #1 Bellerin

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Posted 14 April 2021 - 09:24 AM

Dear all,

I have conducted a popPK model with steady state. In our study, oral drug A is given to subjects once daily for 2 weeks before PK sampling. Then, blood samples are collected at pre-dose and at 1, 2, 4, 6, 8 hours after drug intake. VPC results indicated that final structural model fitted the data well.

I want to use this model for AUC calculation and dose simulation. However, I met some issues when using this steady-state model for AUC calculation, warning some subjects are unable to achieve steady-state. I’m not sure if I have used a right method for AUC calculation. It will be much appreciated if someone can give me some suggestions. I have attached my document. Looking forward to your kind replies!

### #2 smouksassi1

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Posted 14 April 2021 - 12:04 PM

how are you telling the solver that the ODE for AUC is at steady state ?

A straightforward solution is to simulate rich profile and do an nca

and in theory AUC0-tau at ss = AUC infinity = Dose/CL

so you can just compute the model based AUC0-24 at ss

### #3 bwendt@certara.com

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Posted 15 April 2021 - 09:58 AM

There is one trick: you can reset AUC before dosing, e.g. using a dosepoint statement as follows:

dosepoint(Aa, dobefore={AUC=0})

Please see updated project file attached.

Bernd

### #4 Bellerin

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Posted 18 April 2021 - 11:59 AM

how are you telling the solver that the ODE for AUC is at steady state ?

A straightforward solution is to simulate rich profile and do an nca

and in theory AUC0-tau at ss = AUC infinity = Dose/CL

so you can just compute the model based AUC0-24 at ss

Thank you for your reply! I have tried the way as you suggested. It does work.

### #5 Bellerin

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Posted 18 April 2021 - 12:05 PM

There is one trick: you can reset AUC before dosing, e.g. using a dosepoint statement as follows:

dosepoint(Aa, dobefore={AUC=0})

Please see updated project file attached.

Bernd

It's a brilliant method and is time-saving when the work of data analysis is heavy. Many thanks.

### Also tagged with one or more of these keywords: AUC calculation, Dose simulation, Steady state

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