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

----- 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 > > > ----------------------------------------------- > > > > > > > > > > > > >