Bioequivalence and Bioavailability Forum

Dear all,

In bioequivalence studies of endogenous substances, factors that may influence the endogenous baseline levels should be controlled if possible (e.g. strict control of dietary intake)

The USFDA recommendations for 500 mg is to do both a SD fasting and fed studies. Aaccording to the draft guidance, For both the fasting and the fed studies, baseline ursodiol levels at -48, -42, -36, -30, -24, -18, -12, -6, and 0 hours are to be measured before dosing. For the fed study only, a standard breakfast should be administered to the subjects 30 minutes prior to the -48, -24 and 0 hour sample collection time points.

Ursodiol is a secondary bile acid affacting cholesterol absorption. Considering the fact that subjects would be receiving different meals during predose sampling points (breakfast, lunch, snacks , dinner), wouldnt the fat concentration in the meals affect the endogenous ursodiol levels and hence affecting the final mean value taken for baseline correction? If the study is a fasted study, wouldnt standardising the predose sampling after overnight fasting ensure standardisation of predose levels?

Thank you for your comments in advance.