Bioequivalence and Bioavailability Forum

Hi,

❝ In fact I would like to add a situation I have faced in couple of studies for pMDI formulation (with and without charcoal treatment), for Salmeterol I got AUC% extrapolation more than 20 % in about 35 % of the population and most of the subjects achieved either zero concentration much before the last concentration or had very slight concentration at last time point, actually a straight line was seen in the elimination phase because of which although samples were collected sufficient time period (up to 18 hrs post dose), AUC% extrapolation was greater than 20%. Following is a profile typically seen in most of the subjects but we got a query from regulator over it for validity of the as per guideline?

Let me make sure I deciphered your question correctly. 1) Are you talking about BE studies (T vs R)? 2) You said some subjects showed AUClast up to 8 hrs only for both T and R, while some showed AUClast up to a longer collection time? If so, I don't understand your concern. What query would the agency have? I can see the issue if the same subject shows AUC only up to 8 hrs for Test but AUC up to a longer collection time for Reference.

I recently ran a highly variable drug BE study. AUCs were a mess with subjects having

1. undetectable concentration after 4 hr sampling
   
2. undetectable concentrations after 12 hr sampling
   
3. all concentrations above LLQ at end of collection time of 48 hrs.

John