Towards a deeper understanding of physiological factors affecting drug and formulation behavior in the human gastrointestinal tract

Intraluminal profiling is a successful technique which allows you to measure drug concentrations in the gastrointestinal (GI) tract as a function of time by aspiration of fluids in the stomach and upper small intestine (i.e. duodenum). Although these studies assisted us to unravel the intestinal behavior of selected oral medicines, it was not always straightforward to correlate the gastrointestinal behavior of the drug with concentrations appearing in blood. As oral drug absorption even takes place at the more distal parts of the small intestine (i.e. jejunum), it is of paramount importance to profile the drug also in these regions of the small intestine. In addition, there is a lack of knowledge regarding the impact of GI physiology (e.g. motility, pH, and GI fluid composition) on measured drug concentrations. To this end, the proposed project will focus on measuring drug concentrations in the different segments of the GI tract in humans in parallel with examining above-mentioned specific GI variables to evaluate their impact on intraluminal concentrations of the drug and intestinal drug absorption. The multi-dimensional information of drug concentrations and measured impact of the dynamic physiology on these concentrations will serve in the second part of this work as reference data to evaluate and potentially optimize different preclinical tools that are frequently applied to predict the in vivo outcome of a drug in an early stage of oral drug development.