Bioequivalence and Bioavailability Forum

Dear Tina

As Helmut has already mentioned

❝ You have the same ratio for AUC and Cmax, both pointing in the same direction – higher absorption.

Now coming to your specific questions

❝ 1. If it were to be a product issue, would not both parameters be affected?

Yes, most likely it is a product issue. As 116% T/R ratios for Cmax and AUC clearly indicates that there is higher absorption.
How about looking into the formulation details too, for e.g. use of surfactant (Surfactants not only increase solubility but also increase permeability), particle size data (finer particles or so) etc, role and impact of used excipients on invivo performance.

You shall also look into the dissolution data as well, might not get IVIVC but some correlation can be obtained

I need to know few thing to help you in a better way

1. BCS class of the drug /pH solubility profile
   
2. whether the study was fasting or fed?
   
3. Tmax of the molecule

❝ 2. What are the causes for having only failing AUC 0-t?

May be higher Intra subject CV as with the same T/R ratio Cmax is comfortable.

❝ 3. Would increasing sample size (based on variability) to 28 be sufficient to counter the ISV of AUC 0-t?

Already answered by Helmut, You can go ahead if

❝ […] you opt for a crazy sample size of 126 subjects (T/R 116%, CV 24%, 80% power).

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Edit: Standard quotes restored. [Helmut]