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Sixty patients with active distal ulcerative colitis participated in a multicentre randomized double-blind trial to compare the effect of a beclomethasone dipropionate (BDP) enema (3 mg/100 ml) with 5-aminosalicylic acid (5-ASA) enemas (2 g/ 100 ml) and enemas with a combination of BDP/5-ASA (3 mg/2 g/100 ml). The patients were treated for 4 weeks and the efficacy of the drugs was evaluated by sigmoidoscopy, histology and subjective symptoms after that time. The overall results after 28 days of treatment were: clinical improvement 100% (BDP/5-ASA) vs. 70% (BDP) and 76% (5-ASA); endoscopic improvement 100% (BDP/5-ASA) vs. 75% (BDP) and 71% (5-ASA); histological improvement 95% (BDP/5-ASA) vs. 50% (BDP) and 48% (5-ASA). After 4 weeks of treatment seven of 19 patients (37%) receiving BDP/5-ASA had healed endoscopically, compared with six of 20 receiving BDP (30%) and two of 21 receiving 5-ASA (10%). Two patients on 5-ASA and three on BDP had a marked deterioration during treatment. The combination of BDP and 5-ASA was significantly superior to single-agent therapy in terms of both improved sigmoidoscopic and improved histological score. No differences in improvement between the 5-ASA vs. BDP-treated patients were noticed. No side effects were seen. The results of the study show that topical treatment of active distal ulcerative colitis with either 5-ASA or BDP is equally efficacious. So far, no data on topical combination therapy have been described. However, combination therapy with BDP/5-ASA seems superior to single-agent therapy and causes no adverse reactions.

In order to investigate the retrograde spread in the colon and its relationship to the extent of the diseased area, the authors evaluated a 100ml enema of mesalazine (5-aminosalicylic acid, Pentasa') lg in a consecutive series of 30 patients with ulcerative colitis. The enema was labelled with 10 MBq 99mtechnetium-human serum albumin microcolloid. Sequential scintigraphic imaging was performed in all patients, and the results compared with the extension of the disease as found by colonoscopy. If the enema reached the entire affected area it was interpreted as 'topically adequate'. In 80% of the patients there was retrograde spread of the enema beyond the rectosigmoid, thus reaching the affected area in ulcerative colitis. No relationship was found between the extent of dispersion of the enema and the time of defecation prior to scintigraphy. The authors conclude that a 100ml 'Pentasa' enema may be adequate for treatment of ulcerative colitis extending up to the splenic flexure.

In vitro dissolution profiles of three controlled-release mesalazine formulations were determined at pH 1.0, 6.0 and 7.5. A closed-column type dissolution apparatus was used. A reproducible gradual dissolution profile was seen for Pentasa at all pH values. Dissolution starts immediately and is complete after 20 h. Dissolution profiles at pH 1 and pH 7.5 are much alike and dissolution is faster than at pH 6. The behaviour of Asacol at different pH values corresponds with the expectations: no release at pH 6 and pH 1, fast release at pH 7.5. Dissolution starts after 1 h and is complete after 3 h. Mesalazine release from Salofalk tablets at pH 7.5 and pH 6.0 starts after 2 and 3 h, respectively, and is complete after 5 and 10 h. However, after a long lag-time (10 h) mesalazine is also released from Salofalk tablets at pH 1 and dissolution is complete after 23 h.

The mesalazine-containing preparations Asacol, Pentasa, and Salofalk (=Claversal) are frequently used in the treatment of inflammatory bowel disease. The release patterns of these formulations are time- and/or pH-dependent. The aim of this study was to investigate the patterns of absorption of these preparations and the influence of raised intragastric pH on absorption. Gastric pH was raised by simultaneous administration of famotidine. Absorption was determined by assaying with a high-performance liquid chromatography method the urinary excretion of acetylmesalazine, the major metabolite of mesalazine. A large intra- and inter-individual variability in absorption was found for all three formulations, both with and without concomitant famotidine administration. Asacol and Pentasa were significantly less absorbed than Salofalk. A significant lower absorption of mesalazine was seen when Asacol was combined with famotidine. Variations in gastric pH have negligible effect on the bioavailability of mesalazine in vivo.

Twenty-nine patients with attacks of distal ulcerative colitis were treated randomly with 3 g 5-aminosalicylic acid (5-ASA) or 30 mg of prednisolone phosphate sodium (PP) enemas (40 ml). Endoscopic, clinical, and histologic improvement were comparable in the two treatment groups. Our study showed that topical treatment with 5-ASA is as efficacious as PP in improving distal ulcerative colitis.