A pharmacoscintigraphic evaluation of oral budesonide given as controlled‐release (Entocort) capsules

Abstract

SUMMARYAims: 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 111 In 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 ¼ 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 ¼ 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.

A Randomized, Double-Blind, Placebo-Controlled, Phase II Study Comparing the Tolerability and Efficacy of Ipilimumab Administered with or without Prophylactic Budesonide in Patients with Unresectable Stage III or IV Melanoma

“…Possible explanations for the absence of an effect could include an inability of budesonide to suppress inflammation, delivery of budesonide primarily to the small bowel and proximal colon, or insufficient absorption (42). The results from the present study suggest that budesonide should not be used for the prevention of grade ≥2 diarrhea.…”

Gastrointestinal transit, release and plasma pharmacokinetics of a new oral budesonide formulation

“…In particular, inflammation has been reported to significantly affect colon transit, such that ascending colon transit shortens with more drug remaining to be delivered to and absorbed by the distal colon [15]. To what extent inflammation influences mucosal drug absorption of budesonide is currently a matter of debate, as systemic exposure in patients with active Crohn's disease has been described to be either increased or decreased compared with healthy controls [10,13]. Besides inflammation, the absorption of budes-onide might also be affected by the expression of Pglycoprotein, an intestinal efflux pump, which actively secretes substrates into the gut lumen.…”

“…Venous blood samples (10 mL) were collected from an arm vein at predose on days 2, 4, 6 and 7, and at the following time points after the last dose on the 7th treatment day: 0 (predose), 2,3,4,5,6,7,8,10,12,16,20,24,30,36 and 48 h. Plasma samples, obtained by centrifugation were stored at ≤ − 20 ° C until analysis.…”

Pharmacokinetic Behaviors of Orally Administered Drugs

“…Furthermore, higher mean absorption times (MAT) and systemic availability (1.41-and 1.78-fold, respectively) were also observed in patients compared to those in controls. In addition, controlled-release capsules exhibited higher t max , C max , and MAT values compared to the immediate-release standard capsules (Edsbacker et al, 2003).…”