Bioequivalence and Bioavailability Forum

Hi again!

Lately I recognize a trend to increase number of samples in study designs for BE-studies to considerably more than 20 per application even for "simple" IR formulations.

First thought: $$$$ (CRO designs study )

Second thought: Might there be a lower variability e.g. for Cmax with increased number of samples around Cmax (effect on AUC will be lower, in the absence of secondary peaks, I guess)? Gut feeling tells me: Possible. But to a relevant extent? Does increase in number of samples from about 16 (oldschool) to far beyond 20 really buy something regarding "quality" of data?

Isn't there an ethical/practical limit for blood sampling (from the top of my head I remember an absolute limit for blood volume to be taken within a trial...)?

Found some publications on the effect of sampling interval on outcome of BE-studies, but only limited systematic studies on number of samples, especially LSM (limited sampling models) appear to have been hip around year 2000.

Int J Clin Pharmacol Ther. 1999 Jun;37(6):275-81.
A limited sampling approach in bioequivalence studies: application to long half-life drugs and replicate design studies.
Mahmood I1, Mahayni H.

Biopharm Drug Dispos. 2001 Jul;22(5):179-90.
Evaluation of a limited sampling method used to determine the bioequivalence of highly variable drugs with long half-lives.
Jackson AJ

Any opinions/experience/feelings on that?