Re: Distribution of Simulated Cmax

From: bulitta@ibmp.osn.de Subject: Re: [NMusers] Distribution of Simulated Cmax Date: Sat, 19 Nov 2005 18:58:46 +0100 Dear Partha, I would start with a bootstrap re-sampling of the observed Cmax's of your original study. If you generate a few thousand bootstrap pseudo-samples of the same sample size as used in your study, you should get a good idea which degree of similarity in the distribution of Cmax you would expect from a population PK model. As long as you have a reasonable number of subjects in your original study, the most adequate population PK model should provide you similar simulated Cmax distributions as the bootstrap pseudo-samples from the original study. Did you check that the extent of absorption was similar, in case you pooled data from more than one study? Which between and within subject variability from ANOVA statistics did you get from the Cmax of your original study? If you have only a few subjects and a large within subject variability (between occasion variability), then such a formulation might fail to be bioequivalent to itself in a bioequivalence trial. Another idea would be to use a different error model around the expected Cmax region. (Have not tried this myself, but might be worth to try.) Best regards Juergen ---------------------------------------------------------------- Juergen Bulitta, M.Sc. Scientific Employee, IBMP Paul-Ehrlich-Str. 19, 90562 Nuernberg-Heroldsberg Germany