Metrics to Characterize Concentration-Time Profiles in Single- and Multiple-Dose Bioequivalence Studies

In bioequivalence assessment, pharmacokinetic characteristics of concentration-time curves have traditionally been associated with rate and extent of absorption. In the actual context of bioequivalence, however, the similarity of the shapes rather than that of the absorption rates is essential. As a consequence, the following definition of bioequivalence was proposed during Bio-International ‘94 as a more appropriate one: “Two medicinal products are considered bioequivalent if their concentration-time profiles are so similar that they are unlikely to produce clinically relevant differences in therapeutic and/or adverse effects.” In order to quantify the similarity of concentration-time profiles, suitable shape characteristics (metrics) and appropriate bioequivalence acceptance limits (bioequivalence ranges) are needed. Whereas the majority of recent investigations dealt with indirect measures of rate of absorption and their sensitivity to simulated changes in the absorption rate, future research should focus on the similarity of the concentration-time curves rather than that of absorption rates.