Gut delivery of budesonide, a locally active corticosteroid, from plain and controlled-release capsules

To compare the pharmacokinetics and site of uptake of budesonide from a controlled-release formulation and a deuterium-labelled standard formulation given before and after a meal.

Six healthy volunteers were randomized into an open, crossover study. They received 4.5 mg controlled-release budesonide (mixed with In pellets to trace gastrointestinal transit) and 4.8 mg 2H8-budesonide simultaneously at each of two visits: one visit before a standardized breakfast and the other after breakfast. Plasma concentrations of budesonide were followed over 24 h. The transit of the (111)In pellets through the gastrointestinal tract was followed for 36 h. Data on the site of absorption were calculated from transit times and absorption curves.

The time to peak plasma concentration was significantly increased with controlled-release budesonide when compared with the deuterium-labelled standard formulation (before breakfast, 4.5 h vs 1.8 h; after breakfast, 5.2 h vs 2.9 h). When given after breakfast, the controlled-release formulation was associated with a mean residence time 1.6 h longer than that seen with the standard formulation. However, the areas under the plasma concentration curves were similar with the two formulations, regardless of when the treatments were given (before breakfast, 18.0 +/- 3.8 nmol/l vs 18.0 +/- 6.0 nmol/l; after breakfast, 16.9 +/- 7.0 nmol/l vs 18.5 +/- 9.0 nmol/l). Over 60% of the total budesonide absorbed from controlled-release capsules was delivered and absorbed in the ileum and colon. The corresponding proportion for the standard formulation was approximately 33%.

Controlled-release budesonide effectively delivers most of the budesonide dose to the ileum and colon, the regions that are most often affected by inflammatory bowel disease. In addition, the time of food intake has little effect on the site of absorption or the bioavailability of the controlled-release formulation. Delivery to the colon and ileum was independent of whether the drug was given before or after breakfast.