Comparing the concentration curves directly in a pharmacokinetics, bioavailability/bioequivalence study

Abstract

In a traditional pharmacokinetics (PK), bioavailability (BA) /bioequivalence (BE) study, the same number of time points and sampling times are used for each subject. Often, an indirect inference is then made on some PK parameters such as area under the plasma concentration curve (AUC), maximum plasma concentration (C(max)), time to maximum plasma concentration (T(max)) or half-life. However, since these PK parameters are summarized from repeated measurements, a lot of information can be lost. The indirect inferences on some PK parameters are not always accurate. Taking the repeated measurements of the concentration curve into consideration, a functional linear model has been developed to compare concentration curves directly instead of the PK parameters. Considering the nature of repeated measurements, a multiple testing procedure is proposed to assess the equality of two concentration curves. A real data set is used to demonstrate the proposed procedure.