Abstract

To date, mechanistic modeling of oral drug absorption has been achieved via the use of physiologically based pharmacokinetic (PBPK) modeling, and more specifically, physiologically based biopharmaceutics model (PBBM). The concept of finite absorption time (FAT) has been developed recently and the application of the relevant physiologically based finite time pharmacokinetic (PBFTPK) models to experimental data provides explicit evidence that drug absorption terminates at a specific time point. In this manuscript, we explored how PBBM and PBFTPK models compare when applied to the same dataset. A set of six compounds with clinical data from immediate-release formulation were selected. Both models resulted in absorption time estimates within the small intestinal transit time, with PBFTPK models generally providing shorter time estimates. A clear relationship between the absorption rate and the product of permeability and luminal concentration was observed, in concurrence with the fundamental assumptions of PBFTPK models. We propose that future research on the synergy between the two modeling approaches can lead to both improvements in the initial parameterization of PBPK/PBBM models but to also expand mechanistic oral absorption concepts to more traditional pharmacometrics applications.

By Di Wu, Athanasios A. Tsekouras, Panos Macheras & Filippos Kesisoglou