Properties of Metrics Applied for the Evaluation of Bioequivalence

Abstract

Characteristics of metrics are defined in order to assist the effective assessment of bioequivalence as well as the evaluation of metrics and the development of new ones. Metrics should show specificity by reflecting only the kinetic quantity which they are expected to represent. An ideal metric should be linear with respect to the underlying kinetic quantity, and should exhibit high kinetic sensitivity and low statistical responsiveness. The area under the curve for the time course of plasma concentrations (AUC) is demonstrated to have features of an ideal metric. In contrast, C_max (the maximum plasma concentration) is shown to deviate strongly, in all respects, from having ideal characteristics for the assessment of bioequivalence. Notably, the kinetic sensitivity of C_max is not only very low but, as a consequence of nonlinearity, also uncertain.