Evaluation of oral budesonide in the treatment of active distal ulcerative colitis.

Author(s): Kolkman JJ, Mollmann HW, Mollmann AC, Pena AS, Greinwald R, Tauschel HD, Hochhaus G

Affiliation(s): Medisch Spectrum Twente, Enschede, the Netherlands.

Publication date & source: 2004-07, Drugs Today (Barc)., 40(7):589-601.

Publication type: Clinical Trial; Clinical Trial, Phase II; Multicenter Study; Randomized Controlled Trial

Budesonide, a topical corticosteroid, has proven useful for the management of Crohn's disease. Its efficacy is similar to prednisone but it has fewer side effects. A new pH-modified release capsule (Budenofalk) is probably efficacious in distal ulcerative colitis. The aim of the present study was to establish the pharmacokinetics, pharmacodynamics, and safety of two dosage regimens of budesonide capsules and to obtain efficacy information. Budenofalk 9 mg daily was administered as a single dose 9 mg in 8 patients and as three 3 mg doses in 7 patients with active distal ulcerative colitis for 8 weeks. Symptoms were assessed at three timepoints during the study: baseline, 4 and 8 weeks after start of treatment. Endoscopic evaluation and budesonide concentration in mucosal biopsy specimens was performed at 0 and 8 weeks. A pharmacokinetic profile and pharmacodynamic profile (cortisol, lymphocytes and neutrophils) was performed at day 5. In the 9 mg o.d. group, higher peak concentrations and systemic availability was found compared to the 3 mg t.i.d. group. Cortisol suppression was more pronounced after 9 mg o.d. than after 3 mg t.i.d. Lag-time, AUC and pharmacodynamic effects were comparable (14% mean decrease lymphocyte count and 26% mean increase neutrophil count). Mucosal biopsy specimens in the distal colon revealed significant budesonide levels with both regimens. After 8 weeks, 71% in the 9 mg o.d. group and 38% in the 3 t.i.d. group responded. The endoscopic index improved from 10 +/- 2 to 2 +/- 3 (p <0.001) with 9 mg o.d. and from 9 +/- 2 to 4 +/- 4.7 (p = 0.02) with 3 mg t.i.d. The pharmacokinetic and pharmacodynamic profiles found in this study indicate that Budenofalk reaches the distal part of colon and rectum, but further studies to validate the budesonide assay in the mucosa and comparison with a control group are necessary. This limited study suggests that Budenofalk is effective in distal colitis and side effects are rare. Based on these observations a large clinical trial using 9 mg o.d. is indicated to confirm efficacy and assess further possible side effects.