RE: calculation of AUC

From: Mats Karlsson Date: March 21, 2009 technical Source: mail-archive.com
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 _____ No viruses found in this incoming message Scanned by iolo AntiVirus 1.5.6.4 http://www.iolo.com/iav/iavpop3 http://www.iolo.com
Mar 20, 2009 Ethan Wu calculation of AUC
Mar 20, 2009 Michael Fossler Fw: calculation of AUC
Mar 20, 2009 Martin Bergstrand RE: calculation of AUC
Mar 20, 2009 William Bachman RE: calculation of AUC
Mar 20, 2009 Michael Fossler Fw: calculation of AUC
Mar 21, 2009 Mats Karlsson RE: calculation of AUC
Mar 22, 2009 Nick Holford Re: calculation of AUC
Mar 22, 2009 Mats Karlsson RE: calculation of AUC
Mar 24, 2009 Nick Holford Re: calculation of AUC
Mar 25, 2009 Mats Karlsson RE: calculation of AUC
Mar 25, 2009 Yaning Wang RE: calculation of AUC
Mar 26, 2009 Yaning Wang RE: calculation of AUC