The prodrug is conveniently orally-dosed but poorly absorbed in the upper GIT. Furthermore, the low bacterial activity found in the small intestine, prevents the premature release of the parent active principle. This allows most of the dose to reach the lower bowel while minimizing systemic exposure.
Gut Bacterial Activation
The sharp gradient of bacterial activity between the upper GIT and the lower bowel is used as a very specific trigger to bioactivate the prodrug in the colonic area.
Active Principle Release
The enzymatic breakdown of the covalent bound linking the parent anti-inflammatory agent and the promoiety releases the active principle. This local delivery represents the best strategy to avoid systemic immunosuppression while maximizing the drug concentration at the site of inflammation.