Title : Understanding intestinal permeability: The effect of intestine complexity on oral drug absorption
I n this lecture, regional-dependent intestinal permeability will be discussed, including dissolution aspects, as well as pathophysiological conditions. Permeability is location dependent, and pertains to each point throughout the gastrointestinal tract. A drug may exhibit significantly different intestinal permeability not only between the small and large intestine, but even within the small intestine, i.e. between the proximal jejunum and the distal ileum. The asymmetrical pH profile throughout the small intestine may be the underling mechanism for such segmental-dependent permeability of certain ionizable drugs. An asymmetrical expression pattern of different transporters throughout the intestinal tract may also cause such regionaldependent permeability. Asymmetrical intestinal enzymes expression may significantly influence the systemic bioavailability of a drug, although not necessarily affect the permeability. In these cases, rapid vs. sustained dissolving drug products may result unexpectedly different systemic drug levels. In conclusion, it is prudent to consider the intestinal permeability pattern when deciding on a certain dissolution profile.
The audience will learn to consider the intestinal permeability pattern along the whole gastrointestinal tract when deciding on a certain dissolution profile for a given drug candidate; the audience will be able to implement these principles to develop optimal drug exposure following oral administration.