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

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