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Re: Question about interoccation variability

From: Nick Holford <n.holford>
Date: Thu, 12 Jul 2012 06:07:21 -0600


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

> 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

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: n.holford

Received on Thu Jul 12 2012 - 08:07:21 EDT

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