Title:
Physiologically based Pharmacokinetic Models under the Prism of the Finite Absorption Time Concept
Languages of Item:
English
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. © 2022, Merck & Co., Inc., Rahway, NJ, USA and its affiliates under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.
Authors:
Wu, D.
Tsekouras, A.A.
Macheras, P.
Kesisoglou, F.
Journal:
Pharmaceutical Research
Publisher:
Springer-Verlag
Keywords:
dipyridamole; etoricoxib; gaboxadol; losartan; pioglitazone, Article; concentration (parameter); controlled study; drug absorption; drug formulation; drug penetration; drug release; human; intestine transit time; mathematical model; physiologically based biopharmaceutics model; physiologically based finite time pharmacokinetic model; small intestine; time; biological model; computer simulation; intestine absorption; oral drug administration; permeability; pharmaceutics; physiology; procedures; solubility, Administration, Oral; Biopharmaceutics; Computer Simulation; Intestinal Absorption; Models, Biological; Permeability; Solubility
Official URL (Publisher):
DOI:
10.1007/s11095-022-03357-0
