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At least 307 records · Page 17Linked to original sources
PubMed1988

Review: new aminosalicylic acid derivatives for the treatment of inflammatory bowel disease.

Up to 20-30% of patients treated with sulphasalazine experience a variety of adverse effects, principally due to the carrier moiety sulphapyridine. In the last decade there has been a major drive to develop a new generation of 5-aminosalicylic acid (5-ASA) and 5-ASA-related drugs which not only have a high efficacy but are also devoid of the unwanted side-effects of sulphapyridine. Various forms of 5-ASA have been evaluated in ulcerative colitis and appear to be effective orally in preventing relapse and topically in the treatment of active distal colitis. More recently, topical 4-ASA has been found to be useful for the treatment of distal colitis with the advantage of better stability and lower cost compared with 5-ASA. In the foreseeable future it seems likely that these new aminosalicylic acid derivatives will become the drugs of choice in the treatment of inflammatory bowel disease and largely replace sulphasalazine.

Aminosalicylic Acids↗
PubMed1991

[Pancreatitis associated with 5-aminosalicylic acid].

Acute pancreatitis with severe belt-like upper abdominal pain developed within 1-4 weeks of starting medication in three patients (29-year-old man with ulcerative colitis; 43-year-old woman and 22-year-old woman with Crohn's disease) treated, for the first time, with 5-aminosalicylic acid (mesalazine), 500 mg three times daily. Concentrations of lipase initially were 545, 1182 and 3000 U/l, and of amylase 243, 449 and 129 U/l, respectively. Symptoms receded within a few hours after the drug had been discontinued, enzyme levels returning to normal in the course of the next 2-3 weeks. On repeating the drug in two of the patients, in lower dosage, the pancreatitis recurred within a few days. These observations support the view that 5-aminosalicylic acid can cause acute pancreatitis, perhaps as an allergic reaction.

Acute Disease↗
PubMed1994

Interstitial nephritis associated with 5-aminosalicylic acid.

A patient with severe Crohn's disease was treated with 5-aminosalicylic acid (5-ASA). Following initiation of treatment, serum creatinine increased slowly from 105 to 530 mumol/l (creatinine clearance 16 ml/min). The diagnosis of an interstitial nephritis was made based on normal urinary findings and the renal biopsy histology of interstitial mononuclear infiltrates and normal glomeruli, 5-ASA was discontinued and serum creatinine decreased to 245 mumol/l (creatinine clearance 40 ml/min) during the following 3 months. Partial reversibility of renal failure following discontinuation of 5-ASA and the absence of other drugs possibly causing interstitial nephritis suggest a causal relationship between 5-ASA and interstitial nephritis.

Adult↗
PubMed1990

Luminal concentrations of orally ingested 4-aminosalicylic acid as determined by in-vivo equilibrium dialysis.

We measured 4-aminosalicylic acid (4-ASA) levels in faecal water by in-vivo equilibrium dialysis during oral ingestion of drug by two different dose protocols (A and B). In Protocol A, 5 normal subjects ingested 3 g of 4-ASA as the free acid and 20 mg of metaclopromide per day. On Day 5, small dialysis sacs filled with dextran 40 were ingested and the oral drug was continued until the sacs were retrieved from the stool. Protocol B followed the same format except that 3 g of 4-ASA was ingested twice daily and metaclopromide was omitted. In both protocols concentrations of 4-ASA and N-acetylated 4-ASA in sac contents were measured by HPLC. In-vitro dialysis studies showed bi-directional equilibrium was reached within 120 min. During Protocol A, intraluminal concentrations of total 4-ASA ranged from 14.0 to 32.2 mmol/L with a mean of 20.6 mmol/L. With Protocol B, total 4-ASA levels ranged from 20.1 to 41.3 mmol/L with a mean of 33.9 mmol/L. From 90 to 99% of the drug in the dialysates was N-acetylated. These concentrations of total 4-ASA are similar to those of 5-ASA after ingestion of therapeutic doses of sulphasalazine or absorption-resistant formulations of 5-ASA. Thus, oral 4-ASA could have a role in the treatment of inflammatory bowel disease.

Acetylation↗
PubMed1982

[5-Aminosalicylic acid in ulcerative colitis and Crohn's disease (author's transl)].

5-Aminosalicylic acid (5-ASA, 0.5 g t.i.d. as suppository) was administered to 10 patients with ulcerative colitis and 4 patients with Crohn's disease. Both diseases were active despite out-patient pretreatment in 9 cases for at least 6 weeks with sulfasalazine (1.5-3.0 g/d) and corticosteroids. Prior to 5-ASA treatment the activity index according to Best was 241 +/- 85 for the ulcerative colitis patients and 263 +/- 83 for the Crohn's disease patients. After an admission of 4 to 6 weeks treatment with 5-ASA led to a significant decrease (P less than 0.0001) to 43 +/- 38 in the ulcerative colitis patients whereas the decrease in the Crohn group was markedly less to 165 +/- 129 (P less than 0.035). Apart from two patients with Crohn's disease the antiphlogistic effect of 5-ASA could be proven by endoscopy, histomorphology and (or) radiography with an 86% remission rate and by the improved faecal quality (n = 12). The results show that 5-ASA leads to improvement in part only of patients with Crohn's disease, however that all patients with ulcerative colitis respond to this biologically active metabolite. Particularly due to absence of undesirable side effects 5-ASA represents an advantageous possibility for treatment.

Adolescent↗
PubMed1986

5-Aminosalicylic acid enemas in refractory distal ulcerative colitis: a randomized, controlled trial.

5-Aminosalicylic acid (5-ASA), the presumed active moiety of sulfasalazine, has shown clinical efficacy when administered per rectum as initial therapy to patients with distal ulcerative colitis. We report the results of a randomized double-blind trial comparing nightly retention of a 4-g 5-ASA enema with continued administration of hydrocortisone enemas in 18 patients with persistent active distal ulcerative colitis after at least a 3-wk course of treatment with 100-mg hydrocortisone enemas with or without oral sulfasalazine. Continuation of hydrocortisone enemas rather than placebo was used in the control group to reflect the realistic alternative therapy likely to be employed in current practice. Response to therapy was assessed after 3 wk by comparing pretreatment and posttreatment point scores of clinical, sigmoidoscopic, and histological severity. Improvement in clinical score was achieved in seven of nine 5-ASA enema-treated patients versus one of nine hydrocortisone enema-treated patients (p less than 0.05). Sigmoidoscopic and histological improvement generally paralleled clinical improvement. We conclude that in patients with distal ulcerative colitis unresponsive to standard therapy, treatment with 5-ASA enemas results in significant short-term clinical and sigmoidoscopic improvement in a majority of cases. Moreover, a significantly greater number of refractory patients improve when switched to 5-ASA enemas than when continued on standard therapy.

Adult↗
PubMed1983

Disposition of 5-aminosalicylic acid, the active metabolite of sulphasalazine, in man.

The disposition of 5-aminosalicylic acid (5-AS), the therapeutically active metabolite of sulphasalazine (SZ), has been studied in patients with active inflammatory bowel disease, in patients with biliary tract disease and post-operative T-tube drainage, and in healthy volunteers. Subjects were treated 3 times a day either with 5-AS 0.5 g suppositories and a slow-release preparation or with SZ 1 g tid (equivalent to 5-AS 1.14 g/day). Plasma and urine concentrations of 5-AS and its acetylated major metabolite (AcAS) were monitored during one dosing interval. In a cross-over trial in 5 patients with ulcerative colitis no difference, was found in the dose-corrected mean (+/- SD) steady state plasma levels (Css) of 5-AS and AcAS between treatment with 5-AS suppositories (0.10 +/- 0.07 and 0.50 +/- 0.20 micrograms/ml, respectively) and SZ (0.12 +/- 0.14 and 0.67 +/- 0.14 micrograms/ml, respectively). Urinary excretion of total AS (5-AS + AcAS), too, was similar (192 +/- 70 and 179 +/- 79 mg/day) with both forms of treatment. The oral slow-release form of 5-AS produced slightly higher Css in 5 patients with Crohn's disease (5-AS 0.21 +/- 0.22 micrograms/ml; AcAS 0.83 +/- 0.40 micrograms/ml) and in 5 healthy volunteers (5-AS 0.28 +/- 0.14 micrograms/ml; AcAS 1.10 +/- 0.43 micrograms/ml). Urinary recovery of total AS averaged 20 +/- 6% (patients) and 27 +/- 10% (volunteers).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

5-Aminosalicylic acid is a potent inhibitor of interleukin 1 beta production in organ culture of colonic biopsy specimens from patients with inflammatory bowel disease.

Interleukin 1 beta in biopsy specimens from inflamed colonic mucosa of patients with active inflammatory bowel disease was studied. Compared with normal colonic mucosal biopsy specimens, a significantly greater amount of interleukin 1 beta was present in rectal mucosa before (median (range) 4.3 (2.0-11.8) v 119.2 (30.1-286.8) pg/mg; p less than 0.01) and produced during organ culture (39.1 (9.4-106.8) v 97.6 (28.2-991.6) pg/mg; p less than 0.01). Values of interleukin 1 beta after culture correlated with concentrations of thromboxane B2. Organ culture of inflamed biopsy specimens in the presence of 5 aminosalicylic acid and dexamethasone reduced the amount of interleukin 1 beta detected. At the doses studied, 5 aminosalicylic acid also reduced the amount of leukotriene B4 detected after culture.

Adult↗