A pharmacoscintigraphic evaluation of oral budesonide given as controlled-release (Entocort) capsules.
OBJECTIVE
To investigate the gastrointestinal pharmacokinetics of controlled-release (Entocort) and standard budesonide capsules.


METHODS
Six Crohn's disease patients and eight healthy controls were given controlled-release capsules containing budesonide and an inert 111In label, following breakfast. In the patients, a standard capsule containing deuterium-labelled budesonide was given simultaneously. In the controls, on a separate occasion, the controlled-release capsules were given in the fasting state. Gastrointestinal transit was recorded by a gamma camera. Plasma budesonide and deuterium-labelled budesonide were used to estimate drug release, and urine cortisol was used to assess systemic effects.


RESULTS
Budesonide delivery to the ileo-colonic region was significantly greater after the intake of the controlled-release capsules [69%; 95% confidence interval (CI), 54-84] than after the standard capsules (30%; 95% CI, 15-45) (P = 0.005). Fasting had little impact on uptake. The transit and pharmacokinetics of budesonide were similar in both subject groups, although systemic availability was higher in patients (21%; 95% CI, 13-33) than in controls (12%; 95% CI, 10-14) (P = 0.009). Urinary cortisol was, however, similar in both groups.


CONCLUSIONS
A major fraction of budesonide is released in the ileum and throughout the colon, the intended target for the controlled-release formulation. The prandial state has little effect on budesonide uptake.
Edsbäcker
S
S
AstraZeneca Pharmaceuticals LP, Wayne, PA, USA. Staffan.Edsbacker@astrazeneca.com
Bengtsson
B
B
Larsson
P
P
Lundin
P
P
Nilsson
A
A
Ulmius
J
J
Wollmer
P
P
D000284:Administration, Oral; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D019819:Budesonide / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002214:Capsules; D003106:Colon / Q000378:metabolism; D003424:Crohn Disease / Q000000981:diagnostic imaging / Q000188:drug therapy*; D003692:Delayed-Action Preparations; D005243:Feces / Q000737:chemistry; D005260:Female; D005772:Gastrointestinal Transit; D006801:Humans; D006854:Hydrocortisone / Q000652:urine; D007082:Ileum / Q000378:metabolism; D007408:Intestinal Absorption; D008297:Male; D008875:Middle Aged; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D013668:Technetium Tc 99m Aggregated Albumin; D016482:Urinalysis
D000893:Anti-Inflammatory Agents; D002214:Capsules; D003692:Delayed-Action Preparations; D019275:Radiopharmaceuticals; D013668:Technetium Tc 99m Aggregated Albumin; D019819:Budesonide; D006854:Hydrocortisone