Bioequivalence and Bioavailability Forum

Dear All,

Currently, I am working on a prolonged-release tablets single-dose BE study. The Pk sampling follows up to 48 hours, considering around 11 hours half-life of the drug. The pharmacokinetic parameters of interest are Cmax, AUC0-t, AUC0-inf, Tmax, t1/2, Kel and extrapolated AUC. However, additionally partial AUC need to be estimated.

According to the recently published EMA GL "An early partial AUC (0–cut-off t) and a terminal partial AUC(cut-off t-tlast, separated by a predefined cut-off time point, e.g. the half of the dosage interval are recommended, unless otherwise scientifically justified."

In this case, how to select the cut-off time point? Is it AUC0-12h, as we are giving single dose during study?

As per SPC of innovator, reference product has to be taken twice a day, so dosage interval would be 12 hours. Then cut off time point is AUC0-6h (half of the dosage interval)?

Please elaborate how to decide cut-off time in this case?

Thanks in advance.


MMW