Bioequivalence and Bioavailability Forum

Hi,

❝ Situation 1: Situation somewhat similar to yours, where samples were collected up to 36 hrs post dose, but for some of the subjects AUCt could be calculated only up to 8 hrs, for some of the subjects it was up to 16 hrs and for some of the subjects up to 36 hrs.

My opinions (based on what I could gather from your description and the 2nd graph you posted in pre. posting):

1. You meant you had subjects with AUC_t up to 36 hrs for treatment A and AUCt only up to 8 hrs for treatment B (And the AUC_t values are very different?)? Differences in t_1/2 values? What is the pharm/PK property of the molecule? My crystal ball says the molecule may have auto-induction property such that it "enhances" the metabolism enzyme -> If you do a crossover study then you are cooked because the first period treatment would influence the metabolism capability such that the bioavailability of the 2nd period treatment would get reduced. I faced this issue a while back.
   
   
2. Or you meant some subjects had only AUCt upto 8 hrs for both T and R while some subjects had AUCt upto 36 hrs for both T and R? If so, it's just the variability of the drug. If it's a BE study then what's the issue since we are interested in intra-subject comparison.

One question, how's the solubility and permeability of the drug molecule?

❝ Query 2: Since extrapolation is more than 20% how do we justify such situation?

Like Dr_Dan said "How did you compute AUC_inf?"? If I recall correctly it is possible to throw out/conclude AUC_inf as "not defined" due to ridiculous half-life value. How different were the t_1/2 values for this 20% extrapolation data?

Thanks

John