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

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