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Understanding derived parameters following multiple dose administration

multiple dose tau cmax

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#1 DFrancombe

DFrancombe

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Posted 30 April 2021 - 04:11 PM

Hi Forum,

 

Looking for some insight in to the below

 

When running a NCA with multiple dose data, I have a situation where cmax/tmax has not been identified for a particular patient for the final dosing day but AUCtau has been estimated.

 

The concentration_time data are pretty limited, there is only one non-zero value which occurs ~48 h post dose (the dosing interval is 24 h).

 

Since cmax/tmax (albeit a single point) occurs outside the dosing interval, I had assumed this is why these parameters were not reported for this patient but what i'm not then  understanding is then why an AUCtau is reported (regardless of validity being there is a single non-zero value in this profile).

 

I fear I am missing something very obvious

 

[Project file attached, patient in question is B015, Dosing Day 4, Parameter CHOL]

 

Any help very gratefully received!

 

 

Attached Files



#2 Simon Davis

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Posted 02 May 2021 - 11:42 AM

Hi Danielle, I took a look at to your project and I hope the composite image I attach explaines what happened - you're right it is kind of an artefact of this late profiel that is probably not ideal to assess with NCA and you might have more meaningful interpretation if you could build a compartmental model.

Nonetheless, you get a tiny AUCtau since the software looks at the whole profile you have given and then sees that there is a sample quantified at 48h and is therefore able to calculate an AUC0 to Tlast (inthis case 48h) and there fore can see that some tiny fraction of that appears to 'start' the triangle from 23.03h.

If you ran NCA with a dataset truncated at 24h then AUCtau would also be blank. Tmax and Cmax are already explained as such in the help;
Tmax: Time of maximum observed concentration. For steady-state data, based on observations col­lected during the dosing interval, that is, at or after the dosing time, but no later than the dosing time plus Tau, where Tau is the dosing interval. If the maximum observed concentration is not unique, then the first maximum is used.

I agree this seems a little odd but I think it makes sense when you see frm the summary table and the plots how this sliver of AUCtau was 'found'.

Simon.

Attached Thumbnails

  • tiny_AUCtau.jpg

Edited by Simon Davis, 02 May 2021 - 11:44 AM.





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