Re: Question about interoccation variability
Hi Mat,
Yes, I only have oral PK data and as you expected, the introduction of
variability on F didn't improve the fit.
As Nick suggested previously, I also tried different combinations of BSV and
BOV on ka and Tlag using one compartment and two compartment model. The
incorporation of BOV on ka with two compartment Tlag model gave best fitting
compared to other models. But the parameter estimations are problematic, e.g.
RSEs are very big for V and Q. I think the model is overparamerization.
Any comments and suggestions would be appreciated.
Thanks.
Best,
Claire
Sent from my iPhone
Quoted reply history
On Jul 12, 2012, at 9:43 AM, "Mats Karlsson" <[email protected]>
wrote:
> 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
> (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
>
> 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
>
> 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 fax:+64(9)373-7090 mobile:+64(21)46 23 53
> 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