Bioequivalence and Bioavailability Forum

As subject, I would like to know as following.

for example

If the last two sampling time point are 36 and 48 hr and they have plasma concentration with 0.628 and 0.151 ng/ml respectively and LLOQ is 0.250 ng/ml.

In this case, which one I should do between adjust concentration at 48hr to 0.000 ng/ml and adjust it to missing value?

First option, AUC0-48 = AUC0-36 + [(1/2)(48-36)(0.628)]= AUC0-36 + 3.768
and second, AUC36-48 and AUC0-48 can't be calculated because concentration at 48hr is missing.

In my country, the authorize organization suggest the second option I understand them but I don't agree with them because 3 parameters calculated 90% CI are Cmax AUC0-48 and AUC0-inf which have been mention in the protocol, if 24 subjects are enrolled to the study and 11 subjects in period 1 and 9 subjects in period 2 have concentration under LLOQ in time point 48hr. Final, you have only 12 subjects to completely calculate AUC0-48 in both period.

Thanks for your further opinion.

boonchai