Morphofunctional characteristic of the unstirred water layer intestinal epithelium and its role in absorption/bioavailability of drugs (literature review)

The aim of the article – analysis of the main morphological and functional characteristics of intestine epithelium unstirred water layer (UWL) and its role in molecular mechanisms of absorption/bioavailability of orally administered drugs. The method of UWL thickness determination based on effective permeability (Peff) values under various speed of intestinal perfusion flow as well as this indicator importance for solutions absorption determination there was also discussed the process of drugs is discussed absorption in the gastrointestinal tract which is provided by such physical processes as passive diffusion, facilitated diffusion and active transport, involving the UWL, membranes and endothelial tight junctions. The diffusion of small molecules to the cytoplasm is a rather fast process, thus passive transcellular permeability is determined by only the intestinal apical membrane diffusion. The mechanisms of transcellular and paracellular drugs transport in the intestinal epithelium are described. The possible molecular mechanisms of drugs molecules permeability by facilitated diffusion without energy consumption with channel formers and transfer proteins are discussed. The attention was to the active transport process through the enterocyte membrane with the help of transporters against the concentration gradient which is fulfilled with energy consumption due to ATP or other energy supplies. The classification of such transporters is given based an the transport direction (inside the cell – influx, or out off the cell – efflux) and regarding the organic substance transferred. The role of enterocyte enzymatic system CYP3A4 in drugs metabolism processes regulation is mentioned, which can influence their bioavailability. Key words: drugs, absorption, intestine epithelium, unstirred water layer, entherocyte, transcellular transport, intercellular transport