Understanding GI anatomy and Physiology

The human gastrointestinal (GI) tract is a heterogeneous environment designed for the ingestion and digestion of food and fluid and the excretion of waste products.  The different regions of the GI tract have specific functions and their structure and physiology vary accordingly.  As a consequence, oral drug products are exposed to a dynamic environment.  Changes in surface area, fluid volume and composition, pH, contractile activity, enzyme and transporter concentrations all have the potential to impact on drug dissolution, permeability and gut wall metabolism and hence impact on bioavailability.  

The small intestine is approximately 6 meters in length and can be divided into the duodenum (~30cm), jejunum (~2.4m) and ileum (~3.6m). It is the primary region for the absorption of nutrients and, as such, has an extremely high surface area.  pH ranges from 6.6 in the proximal small intestine to 7.5 in the terminal ileum and fluid content and contractile activity are relatively high.  In comparison, the colon is primarily designed for the absorption of water, followed by storage of waste materials.  It is approximately 1.25m in length and has a much smaller surface area than the small intestine.  A drop in pH is observed when moving from the terminal ileum into the caecum (6.4) followed by a steady rise to pH 7 in the distal regions of the colon.  Fluid volume is substantially reduced and contractile activity is less pronounced.

The expression patterns of enzymes (e.g Cytochrome P450’s) and transporters (e.g PEPT1) changes across different regions of the GI tract, resulting in concentration gradients that can have a profound impact on drug absorption. The magnitude of these effects are typically compound specific, and any formulation strategy designed to deliver an optimised drug product must take these into account.