Bioequivalence and Bioavailability Forum

Dear all,

I would like to open again a new thread regarding endogenous compounds in BE assessments.

Simple case:

- assuming no circadian rhythm / temporarily constant
- baseline subtraction method (e.g. median of at several pre-dose samples)

Several guidelines mention that a negative pre-dose corrected value should be set to zero. However, what about subsequent levels?

I think setting also all concentrations after the first negative to zero would make some sense as otherwise we just have “noise” in the AUC (i.e. increase variability) and it’s rather impossible to get a reliable estimate for lambda_z (for calculation of AUC0-inf). I think this should be also in-line with guidelines as the method for baseline subtraction needs to be specified a-priori.

Best regards and looking forward to thoughts from more experienced members in this forum

Martin

PS.: premise of stable endogenous could be verified by looking at adjusted concentrations after the first negative (inclusive) adjusted concentration: should be symmetrically distributed around zero.