RE: Question about interoccation variability
Dear Claire,
If you have data only from oral doses and covariances between disposition
parameters (CL; V), then you will not get any further improvement by
introducing variability in F1.
Best regards,
Mats
Mats Karlsson, PhD
Professor of Pharmacometrics
FIRST WORLD CONFERENCE ON PHARMACOMETRICS, 5-7 September 2012, Seoul (
http://www.go-wcop.org/ www.go-wcop.org)
Dept of Pharmaceutical Biosciences
Faculty of Pharmacy
Uppsala University
Box 591
75124 Uppsala
Phone: +46 18 4714105
Fax + 46 18 4714003
From: [email protected] [mailto:[email protected]] On
Behalf Of Xu, Claire
Sent: 12 July 2012 15:11
Cc: nmusers
Subject: Re: [NMusers] Question about interoccation variability
Hi Nick,
Thanks for your helpful comment. I will test BOV + BSV on my absorption
model parameters first.
Sorry for my typo. I meant neither of the models improved the fit.
Thanks again for your help.
Best,
Claire
Quoted reply history
On Thu, Jul 12, 2012 at 8:07 AM, Nick Holford <[email protected]>
wrote:
Claire,
See below:
On 11/07/2012 9:45 p.m., Xu, Claire wrote:
Hi Nick,
Thank you a lot for clarifying how to incorporate BOV in the model.
I tested BOV on F1 with the same option as well as variable BOVs on F1 from
different occasions. But either of them improved the fitting.
I am not sure what you mean here. Do you mean that NEITHER of them improved
the fit? If that is the case then it would be compatible with your other
observation that AUC is very similar across occasions which suggests that
there is negligible BOV in CL or F. I find that a bit surprising but it is
not impossible.
Actually according to the results from non-compartmental analysis, AUC0-inf
are very similar across different occasions, while a trend of difference in
Cmax and Tmax was observed. Do you think that more complex absorption models
would help?
Because you are do see BOV in Cmax and Tmax then it seems you should try to
focus on looking for BSV+BOV on your absorption model parameters (Ka, Tlag).
Of course you can also work on the absorption model structure as well.
Open to any comments.
Thanks again for your great input.
Best,
Claire
--
Nick Holford, Professor Clinical Pharmacology
First World Conference on Pharmacometrics, 5-7 September 2012
Seoul, Korea http://www.go-wcop.org http://www.go-wcop.org/
Dept Pharmacology & Clinical Pharmacology, Bldg 505 Room 202D
University of Auckland,85 Park Rd,Private Bag 92019,Auckland,New Zealand
tel:+64(9)923-6730 <tel:%2B64%289%29923-6730> fax:+64(9)373-7090
<tel:%2B64%289%29373-7090> mobile:+64(21)46 23 53
<tel:%2B64%2821%2946%2023%2053>
email: [email protected]
http://www.fmhs.auckland.ac.nz/sms/pharmacology/holford
--
Xu, Claire
Ph.D Candidate
Division of Clinical Pharmacology, Wishard Hospital
Indiana University School of Medicine
1001 West 10th Street, Myers W7122
Indianapolis, IN 46202
T - 317/7558242