Bioequivalence and Bioavailability Forum

Dear all,

at the “EUFEPS BABP Network Open Discussion Forum” members of EMA’s PK-group unambigiously made clear what they mean by C_min in steady state, namely the concentration at the end of the dosing inter­val. See also the presentation (slides 31–34) by Christoph Baumgärtel (AGES, raporteur for the MR-GL). See also a previous thread.

It’s important to check your software. If you use PHX/WNL, forget Cmin, Cavg, and Fluctuation% in the output – which are based on the global minimum within the dosage interval. I’ll ask Pharsight for an update – please do so as well, in order to speed things up.
In the meantime consider setting up a workaround by two Custom Column Transformations (to NCA Results, Final Parameters Pivoted):
New Column Name Tau
Formula          24 ← the numeric value of the dosing interval

New

New Column Name PTF
Formula          100*(Cmax-Clast)/(AUCtau/Tau)

I have no idea yet how to deal with missing values at the end of the dosing interval (t_last # τ). If you are able to estimate λ_z and tick [×] Intermediate Output in the Model Settings of NCA you get additionally the intercept (in log-scale) of the regression – which would allow to calculate an estimated Ĉ_min value at t=τ. But this value is only given in the Core output (not available as a variable in the NCA Results)…