Disease relevance of Azodisal

• Azodisal sodium in the treatment of ulcerative colitis. A study of tolerance and relapse-prevention properties [1].
• When the colitis activity at study entry was compared with that observed at the completion of the study period, statistically significant or nearly significant improvement was demonstrated within the combined olsalazine group (p = 0.01) and within patient groups receiving olsalazine at daily doses of 1.5 g (p = 0.04) and 3 g (p = 0.055) [2].
• Analysis restricted to 64 patients still in remission at 1 year and 18 with relapses also showed a significant difference in relapse rate (olsalazine 5/42 [12%] vs mesalazine 13/40 [33%]; p = 0.024) [3].
• Four patients were withdrawn because of adverse reactions: 2 developed a skin rash while receiving olsalazine and 2 had diarrhea, one while on olsalazine and the other while on placebo [2].
• RESULTS: No differences in the frequency of termination due to relapse or time to termination due to relapse were noted between the two treatment groups (olsalazine 48.5% v placebo 45%) for either colitis or ileocolitis [4].

High impact information on Azodisal

• Mesalazine versus olsalazine for prophylaxis of ulcerative colitis relapse [5].
• METHODS: The General Practice Research Database (GPRD) which contains the primary care records of five million people in the UK was used to identify users of mesalazine, balsalazide, olsalazine, or sulfasalazine with a history of IBD [6].
• 5-Aminosalicylic acid (5ASA), 4ASA, their N-acetylated metabolites N-acetyl-5ASA and N-acetyl-4ASA, olsalazine, and colchicine impair interferon-gamma (IFN gamma) induced HLA-DR expression on a colonic cell line, HT-29 [7].
• Prophylactic effects of olsalazine v sulphasalazine during 12 months maintenance treatment of ulcerative colitis. The Danish Olsalazine Study Group [8].
• In the ileum olsalazine at 0.5 and 1 g/l significantly inhibited glucose uptake (p less than 0.04) and water absorption (p less than 0.03) [9].

Chemical compound and disease context of Azodisal

• Two hundred and twenty seven patients (118 men) with at least two previous attacks of ulcerative colitis were randomly allocated according to a prearranged treatment schedule to olsalazine 500 mg bd or sulphasalazine 1 g bd in a double blind, double dummy fashion [8].
• A patient with refractory Crohn's disease had two separate episodes of bone marrow suppression while receiving 50 to 75 mg 6-mercaptopurine a day and 1000 to 1750 mg olsalazine a day [10].
• Endogenous antioxidant status in neoplastic and adjacent tissues in 1,2-dimethylhydrazine-induced colon cancer in rats: effects of olsalazine [11].
• A prospective randomized observer-blind 2-year trial of azathioprine monotherapy versus azathioprine and olsalazine for the maintenance of remission of steroid-dependent ulcerative colitis [12].
• One patient was receiving SSZ for Crohn's disease and was subsequently treated with olsalazine, which lacks the sulfapyridine component of SSZ [13].

Biological context of Azodisal

• Longterm olsalazine treatment: pharmacokinetics, tolerance and effects on local eicosanoid formation in ulcerative colitis and Crohn's colitis [14].
• Olsalazine 250 mg four times daily significantly accelerated gastric emptying (mean +/- SD; 45.3 +/- 24.2 min v 67.3 +/- 33.1 min, p less than 0.05), mouth to caecum transit time (242 +/- 41 min v 325 +/- 33 min, p less than 0.02) and whole gut transit time (60.5 +/- 26 h v 37.8 +/- 17.8 h, p less than 0.05) [15].
• Neither parent compound (SAZ, olsalazine) nor the pharmacologically inactive metabolite (SP) were effective in attenuating the lipid peroxidation at concentrations up to 100 microM [16].
• We found that the concentrations necessary to inhibit the N-nitrosation reaction by 50% (IC50) were 25, 50 and 100 microM for 5-ASA, olsalazine (dimeric 5-ASA) and sulfasalazine, respectively [17].
• METHODS: The local and systemic bioavailability of 5-ASA from a controlled release 5-ASA preparation (Pentasa--2, 4 or 6 g/day) was investigated and compared with the azo-bond 5-ASA preparation olsalazine (Dipentum--2 g/day) in 13 healthy volunteers during steady state conditions [18].

Anatomical context of Azodisal

• Azodisal sodium is a highly effective means of oral delivery of 5-amino-salicylic acid to the colonic mucosa [19].
• Effects of olsalazine in the jejunum of the rat [20].
• Sulphasalazine, olsalazine and 5-ASA were potent inhibitors of macrophages chemotaxis to LTB4 with IC50 values of 0.43, 0.39 and 0.24 mM, respectively [21].
• The effect of sulfasalazine and olsalazine on the transport of [3H]folic acid and of [3H]methotrexate (MTX) was investigated in organ-cultured endoscopic biopsy specimens of small intestinal mucosa from normal subjects [22].
• Disposition of olsalazine and metabolites in breast milk [23].

Associations of Azodisal with other chemical compounds

• In a double blind, placebo controlled crossover study, comprising eight similar volunteers, ileostomy fluid output increased (p less than 0.05) in a dose related manner during intake of azodisal sodium (1 g/day vs 2 g/day) compared with placebo or sulphasalazine (2 g/day) [19].
• We suggest that the patient's relatively low baseline level of TPMT activity was inhibited by olsalazine and olsalazine-O-sulfate, leading to decreased clearance of 6-mercaptopurine and its accumulation [10].
• In vitro enzyme kinetic studies confirmed the hypothesis that olsalazine and olsalazine-O-sulfate are potent noncompetitive inhibitors of recombinant human TPMT [10].
• 5-Aminosalicylate (5-AS) can be delivered to the colon either by azo-prodrugs (e.g. sulfasalazine, olsalazine or balsalazide) or by direct rectal administration of 5-AS in form of enemas, foam or suppositories [24].
• Azodisalicylate (azodisal sodium) causes intestinal secretion. Comparative study of the effect of azodisalicylate, sulfasalazine, 5-aminosalicylic acid and sulfapyridine on the water and electrolyte transfer and the morphology of the rat ileum and colon in vivo [25].

Gene context of Azodisal

• Olsalazine treatment significantly (P < 0.01) reduced the elevation in glutathione peroxidase activity in neoplastic tissues of rats treated with the carcinogen [11].
• Neither carcinogen nor olsalazine treatment caused alterations in activity of glutathione reductase in adjacent tissue as compared with corresponding control values [11].
• Further study of olsalazine and direct comparison with SASP in this population may illuminate mechanisms of drug action and add a new therapeutic option [26].
• Olsalazine in ankylosing spondylitis: a pilot study [26].
• Pancreatitis associated with olsalazine and sulfasalazine in children with ulcerative colitis [27].

Analytical, diagnostic and therapeutic context of Azodisal

• Olsalazine is not superior to placebo in maintaining remission of inactive Crohn's colitis and ileocolitis: a double blind, parallel, randomised, multicentre study [4].
• A comparison between these clinical and endoscopic parameters at study entry and those at study completion (within drug evaluation) showed significant improvement in six of 10 parameters during treatment with olsalazine and in two of 10 during placebo treatment [28].
• Influence of olsalazine on gastrointestinal transit in ulcerative colitis [15].
• In preliminary experiments, which comprised 10 healthy volunteers treated with colectomy for ulcerative colitis, ileostomy fluid output increased (p less than 0.001) during oral intake of azodisal sodium (1 g/day) [19].
• RESULTS: Mean steady-state plasma concentrations of 5-ASA and Ac-5-ASA were significantly higher after treatment with mesalazine than with olsalazine (P < 0.0001) [29].

References