Modeling the Double Peak Phenomenon in Drug Absorption Kinetics: The Case of Amisulpride

Abstract

An interesting issue observed in some drugs is the “double peak phenomenon” (DPP). In DPP, the concentration-time (C-t) profile does not follow the usual shape but climbs to a peak and then begins to degrade before rising again to a second peak. Such a phenomenon is observed in the case of amisulpride, which is a second-generation antipsychotic. The aim of this study was to develop a model for the description of double peaks in amisulpride after oral administration. Amisulpride plasma C-t data were obtained from a 2 × 2 crossover bioequivalence study in 24 healthy adult subjects. A nonlinear mixed-effects modeling approach was applied in order to perform the analysis. Participants’ characteristics, such as demographics (e.g., body weight, gender, etc.), have also been investigated. A model for describing the double peak phenomenon was successfully developed. Simulations were run using this model to investigate the impact of significant covariates and recommend appropriate dosage regimens. For comparison purposes and to investigate the suitability of our developed model for describing the double peak phenomenon, modeling of previously published population pharmacokinetic models was also applied to the C-t data of this study.