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Re: Improved absorption profile by forcing v olume of the central compartment

From: Jurgen Bulitta <jbulitta>
Date: Tue, 24 Apr 2007 21:03:01 +0200

Dear Brenda,

Just a couple of comments and questions:
1) Is there a specific reason why you are using FO for a dataset with
frequent sampling? How large is your between subject variability?
I would recommend considering FOCE+I in your case (for a more
detailed assessment, see e.g. Bauer R et al. AAPS J. 2007;9:E60-83.)

2) Have you tried a 3 compartment model? I would try this, as you
potentially have frequent observations during the absorption phase.
The number of compartments depends on the rate of absorption,
sampling frequency, and (sometimes) method of analysis. So I would
not worry too much, if you get something else than other reports in literature.

3) I would recommend running visual predictive checks for each group
of patients to check, if you have adequate predictive performance in
each group. The parameter variability model could be one reason,
why you observe better individual fits but a worse objective function
when you fix the volume. In addition, you could prepare some boxplots
for the eta distributions in each group.

4) Did you try some of the models described by Dr. Nick Holford in his 1992
cefetamet pivoxil paper? (J Pharmacokinet Biopharm. 1992;20:421-42.)

5) Sometimes, using a full variance covariance matrix for the absorption
parameters improves the predictive performance during the absorption
phase notably.

Hope some of this will work (-:
Best regards

Juergen Bulitta, PhD, Post-doctoral Fellow
Pharmacometrics, University at Buffalo, NY, USA
Phone: +1 716 645 2855 ext. 281, j

Received on Tue Apr 24 2007 - 15:03:01 EDT

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