RE: calculation of AUC
Dear Ethan,
Just a caution when comparing model-based AUCs with NCA calculated AUCs. If you
have done your modeling using log-transformation of observations and model
predictions and then compared AUCs on the linear scale, you should not expect a
perfect agreement between the two. The reason is that the mean of an
exponentiated distribution of epsilons is not the same as the median, but
higher. Thus, the AUCs of model-predicted individual profiles will be expected
to be lower than either simulated or observed. The magnitude of the difference
will depend on the residual error magnitude and will typically be:
%RV expected AUC difference
10 0.50%
20 2%
30 5%
40 9%
50 14%
70 29%
Best regards,
Mats
Mats Karlsson, PhD
Professor of Pharmacometrics
Dept of Pharmaceutical Biosciences
Uppsala University
Box 591
751 24 Uppsala Sweden
phone: +46 18 4714105
fax: +46 18 471 4003
Quoted reply history
From: [email protected] [mailto:[email protected]] On
Behalf Of Ethan Wu
Sent: Friday, March 20, 2009 6:52 PM
To: [email protected]; [email protected]
Subject: Re: [NMusers] calculation of AUC
sorry for being lazy this morning and wish relying on others knowledge
just to share, I used DADT=C method, and it didn't depend on sampling after I
tried with my model (which took quite a while to get results)
-- I could do as Bill suggested setting up some small dataset and simple model
to check first, then would share with the group ealier :-)
_____
From: "[email protected]" <[email protected]>
To: [email protected]
Sent: Friday, March 20, 2009 9:42:59 AM
Subject: Fw: [NMusers] calculation of AUC
I second Bill's suggestion to work this out on your own for your specific
problem. This forum can help you with general questions and overall approaches,
but very specific queries like this are for you and your colleagues to hash
out.
Error! Filename not specified.
----- Forwarded by Michael J Fossler/PharmRD/GSK on 03/20/2009 09:40 AM -----
"Bill Bachman" <[email protected]>
Sent by: [email protected]
20-Mar-2009 09:17
To
"'Martin Bergstrand'" <[email protected]>, "'Ethan Wu'"
<[email protected]>, [email protected]
cc
Subject
RE: [NMusers] calculation of AUC
The easiest answer is to work it out. Do some simulations (without
variability) with multiple subjects with identical PK parameters BUT different
sampling times. Tabulate your AUCs and compare the results for different
sampling times!
_____
From: [email protected] [mailto:[email protected]] On
Behalf Of Martin Bergstrand
Sent: Friday, March 20, 2009 8:45 AM
To: 'Ethan Wu'; [email protected]
Subject: RE: [NMusers] calculation of AUC
Dear Ethan,
You need to provide more information on how you plan to calculate AUC otherwise
the question can’t be answered. It is of course possible to calculate the AUC
without any influence of the sampling frequency. You should be able to find
examples of how to do this in the NMusers archive. See for example the answer
from Mats Karlsson in this thread (
http://nonmem.org/nonmem/nm/98apr032002.html
http://nonmem..org/nonmem/nm/98apr032002.html).
Kind regards,
Martin Bergstrand, MSc, PhD student
-----------------------------------------------
Department of Pharmaceutical Biosciences,
Uppsala University
-----------------------------------------------
P.O. Box 591
SE-751 24 Uppsala
Sweden
-----------------------------------------------
<mailto:[email protected]> [email protected]
-----------------------------------------------
Work: +46 18 471 4639
Mobile: +46 709 994 396
Fax: +46 18 471 4003
From: [email protected] [mailto:[email protected]] On
Behalf Of Ethan Wu
Sent: den 20 mars 2009 13:05
To: [email protected]
Subject: [NMusers] calculation of AUC
Hi all, to calculate AUC of one of the compartments using ADVAN6, if it is a
fixed time interval, will the AUC be influenced by the frequncy of sampling of
the dataset within this interval or not?
thanks
_____
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