OPTIMAL SAMPLING TIMES IN BIOEQUIVALENCE TESTS

Abstract

In bioequivalence studies, drug formulations are compared in terms of bioavailability parameters such as the area under the concentration-time curve (AUC), the maximum concentration (Cmax), and the time to maximum concentration (t(max)). Accuracy in measuring these parameters directly affects the accuracy of bioequivalence tests. Because the number of blood draws per patient is limited, the blood collection times must be spaced so that concentration-time curve measurements can produce accurate bioavailability parameter estimates. This paper describes an optimization approach for calculating optimal time designs for one-compartment models, but is sufficiently general for other compartmental models. Simulation indicates that the optimal design improves the accuracy of AUC estimation.