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

From: nonmem
Date: Tue, 08 May 2007 13:52:14 +0000 (GMT)

Hello Leonid,

More complex NONMEM methods may need more observations. This is my expirience, but I am glad to find out more about that.

Regards,
Pavel

----- Original Message -----
From: Leonid Gibiansky
Date: Monday, May 7, 2007 3:43 pm
Subject: Re: [NMusers] Improved absorption profile by forcing volume of the central compartment
To: nonmem
Cc: nmusers

> "The method with interaction does not work due to the small
> sample size."
>
> I do not think that this is correct. Sample size should not be
> an issue for FOCEI. If you have lag
> time with random effect, this could be a problem for FOCE, but
> not the sample size.
> Leonid
>
> nonmem
> > 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,
> > Pavel
> >
> > ----- 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 Tue May 08 2007 - 09:52:14 EDT

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