Bioequivalence and Bioavailability Forum

Hi Jag,

❝ Just out of curiosity. Has anyone seen a BE study failing due to AUCinf falling outside 80-125% and the variability in the results seem to be attributed to the determination of Kel (jumpy concentrations)? Sampling timepoint setup was adequate in terms of capturing the terminal eleminaition phase of the PK profile. I wonder if there is any way to save this study.

I have occasionally seen this with drugs requiring very low LLOQs such as inhalation drugs. It seems to me like the assays sometime underperform slightly near the LLOQ in spite of bioanalytical assays with reported scatter at LLOQ within acceptable limits.
Check your ISRs at or near the LLOQ and contrast them with the rest. How does it look?
You may sometimes trigger an audit and have the opportunity to eliminate subjects for whom manifest trouble have been observed but you need a better reason than just a desire to get rid of bad values. Also, it sounds like you may argue that variability is the problem (cf. "jumpy" concentration in the elimination phase) and therefore the study was not adequately powered in terms of AUCinf so you can repeat it with Barbara D's blessing.