Physiological Dynamics in the Upper Gastrointestinal Tract and the Development of Gastrointestinal Absorption Models for the Immediate-Release Oral Dosage Forms in Healthy Adult Human

Abstract

This review is a revisit of various oral drug absorption models developed in the past decades, focusing on how to incorporate the physiological dynamics in the upper gastrointestinal (GI) tract. For immediate-release oral drugs, GI absorption is a critical input of drug exposure and subsequent human body response, yet difficult to model largely due to the complex GI environment. One of the biggest hurdles lies at capturing the high within-subject variability (WSV) of bioavailability measures, which can be mechanistically explained by the GI physiological dynamics. A thorough summary of how GI dynamics is handled in the absorption models would promote the development of mechanism-based oral drug absorption models, aid in the design of clinical studies regarding dosing regimens and bioequivalence studies based on WSV, and advance the decision-making on formulation selection.

Keywords: gastrointestinal dynamics; intra-individual variability; machine learning; oral absorption model; within-subject variability.