Drug Permeability and Metabolism in the Gut

Dear Colleagues,

The gut is the key organ for the absorption of water and nutrients as well as for drug metabolism and absorption. The gut consists of several regions, including the stomach, the small intestine (encompasing duodenum, jejunum, and ileum), and the large intestine. The microenvironment in these regions and even conditions within each region itself rely largely on parameters such as the luminal pH, mucus properties, fluid composition, tight junctions, different intestinal morphologies throughout the gut, microbiota, and many others; it is also well known that there are clear differences in the expression profile of drug transporters and metabolising enzymes along the intestinal tract. All of these, alone or in combination, influence the fate of the drug following oral administration and lead to variable drug absorption, pharmacokinetic (PK) and consequently pharmacodynamic (PD) profiles.

Intestinal permeability is a crucial factor for orally administered drugs, and can in some cases be assisted by uptake transporters or limited by efflux transporters and metabolic enzymes in the gut. It is crucial to identify gut enzymes that induce the biotransformation of orally administered drug molecules as well as intestinal transporters and their pharmacokinetic, pathophysiological, and pharmacogenetic roles in drug transport. Besides scenarios where regional-dependent intestinal permeability occurs, lately, regional differences in human intestinal drug metabolism have been identified as well. Aside from the gut microevironment, these processes are often influenced by the food intake as well as the subject’s age, race, disease status, and BMI.  While drug metabolism in the liver has been widely researched, the pharmaceutical research has further to go in terms of adopting a standardised approach for the characterisation and quantitative prediction of intestinal metabolism. In terms of the development of oral drug candidates, a detailed assessment of intestinal metabolism in the context of typical DMPK activities within the drug-discovery programmes all the way to candidate drug nomination is needed. In this Special Issue, work which focuses on intestinal drug permeability as well as intestinal metabolism is of great interest. Authors are welcome to contribute both original research and review articles.

Dr. Milica Markovic
Guest Editor

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