4 replies to this topic

[Bellerin]

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!

Attached Files

•  Drug A.phxproj   6.5MB   222 downloads

[smouksassi1]

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

[bwendt@certara.com]

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

 Drug A._bwphxproj.phxproj   7.31MB   518 downloads

[Bellerin]

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.

[Bellerin]

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

Drug A._bwphxproj.phxproj

 

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