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Re: Re: Improved absorption profile by forcing volume of the central compartment

From: nonmem
Date: Mon, 07 May 2007 18:55:28 +0000 (GMT)

Hello Brenda,

Your sample looks small.

I have 38 subjects with rich data. FO method works, but plots for sume subjects do not look very good and there are few local maxima. The method with interaction does not work due to the small sample size. Although the prelimenary data are useful, nothing can make the plots perfect. I have to increase the sample size.

Try to run the model for each subject without population estimates. It will give you an idea how the first order approcximation affects your plots.

Try to play with the model of error. If your doses are very different, you may need to use CV+additive model.

Try to implement correlation between Cl and V2, but set correlation between Ka and the other parameters to zero.

Good luck,

----- Original Message -----
From: Jurgen Bulitta
Date: Tuesday, April 24, 2007 3:47 pm
Subject: Re: [NMusers] Improved absorption profile by forcing volume of the central compartment
To: "B.C.M. Winter - De" , nmusers

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

Received on Mon May 07 2007 - 14:55:28 EDT

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