Bioequivalence and Bioavailability Forum

Dear kvitamin,

❝ I understand (?) that there is only one intra-subject CV for each PK parameters (e.g. AUC0-t), because each subjects get both formulas, so the intra-CV gives information about the variability of subjects AUC0-t in formulas point of view.

I do not understand (this).
The intra-subject CV from a classical 2x2 cross-over design is a pooled intra-subject variability for both formulations under study.
A separation in formulation specific values (for Test and Reference) is not possible within the 2x2 cross-over. It needs generally replicate designs in which each formulation is applied more then once at same subject.

❝ But inter-CV get information about the variability of subjects AUC0-t for formulas in separated way: one inter-subject CV for the T formula and one other for the R formula. It is right idea or not?

Not. If you analyze f.i. AUC for Test and Reference separately you will get the total variability, a sum of within-subject and between-subject variability:
s²_T=s²_between,T+s²_within,T for Test
s²_R=s²_between,R+s²_within,R for Reference

If you are not able to separate the intra-subject variability for Test and Reference, how will you estimate formulation specific between-subject variabilities?

Within the average bioequivalence framework all these variabilities are of no especial interest because you have to show only that the means (ratios) of the PK metrics are equivalent.