Emeritus Professor University of Athens Athens, Attiki, Greece
The current FDA and EMA bioequivalence (BE) guidelines utilize the gold standard metric for the extent of absorption, namely, the area under the blood drug concentration curve extrapolated to infinite time (AUC)0-∞. Although, (AUC)0-∞ is an ideal exposure metric, it implies infinite time for absorption, which never happens in the real world; recent findings relying on the finite absorption time (F.A.T.) concept clearly show that absorption terminates at finite time, τ (1, 2). These findings call for a re-assessment of BE studies using the ratio of cumulative areas under the curves (∑▒〖[AUC]_(t_(i-1))^(t_i ),T〗)/(∑▒〖[AUC]_(t_(i-1))^(t_i ),R〗) as a function of the sampling time points (ti) of the study for test T, reference formulation R. This plot becomes a horizontal line beyond time, τ. Therefore, the corresponding ratio [(AUC)0- τ]T/[(AUC)0- τ]R is the ideal metric for the extent of drug absorption. Current recommendations for the sampling schedule beyond time, τ should be abolished.
Learning Objectives:
Upon completion, participant will be able to re-assess BE studies using the ratio of the cumulative areas as a function of sampling time points for the test and reference formulation.