Clinical Evidence Supporting the Radical Scavenger Mechanism of 5-Aminosalicylic Acid

Ahnfelt-Rønne, I.; Nielsen, Ole Haagen; Christensen, Anne‐Lise; Langholz, Ebbe; Binder, Vibeke; Riis, P

doi:10.1016/0016-5085(90)90329-y

Cited by 217 publications

(75 citation statements)

References 29 publications

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“…Possible therapeutic act ions include modulation of the inflammatory response through effects on leukotriene synthesis (6,7) rather than through effects on prostaglandin synthesis (8). Recently evidence has been presented suggesting that 5-ASA is an effective free radical scavenger and that it breaks the free radical chain reaction (9).…”

Section: Discussionmentioning

confidence: 99%

A Double-Blind, Placebo Controlled, Multicentre Study of the Efficacy And Safety of 5-Aminosalicylic Acid Tablets in the Treatment of Ulcerative Colitis

Sutherland¹,

Mg²,

Onstad³

et al. 1990

Canadian Journal of Gastroenterology

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This double-blind, placebo controlled, multicentre, parallel trial assessed the efficacy of two oral doses of a new formulation of 5-aminosalicylic acid (5-ASA) targeted to release in the cecum which was given for six weeks to 136 patients with active ulcerative colitis. Seven centres participated (two Canadian, five American). Patients were randomly assigned to one of three treatment groups (4 g 5-ASA, 2 g 5-ASA or placebo). Medication was dispensed as 250 mg identically appearing tablets containing either 5-ASA or placebo to be taken four times a day. Subjects were assessed at baseline and after three and six weeks of treatment. Assessments included a disease activity index, physician's global assessment and flexible sigmoidoscopy. Compliance was assessed through pill count. A total of 136 patients participated ( 4 7 on 4 g 5-ASA, 45 on 2 g 5-ASA, and 44 on placebo). The three groups were similar in terms of age, weight, distribution of disease, extent of disease, and previous use of steroids or sulphasalazine. Ninety patients completed the six week study. Of the 46 dropouts, 38 (82.6%) left because of insufficient efficacy ( most on either place ho or 2 g 5-ASA), four (8.7%) had adverse reactions (all on 5-ASA), the remaining four (8.7%) left for reasons not related to their ulcerative colitis. The disease activity index represents a composite score ( maximum of 12) with categories for number of daily stools, presence of bleeding, abdominal pain and physician's assessment of disease activity. Patients who received 4 g 5-ASA daily demonstrated significant declines in disease activity index within three weeks of therapy and maintained improvement until the end of the stuuy. Although disease activity index declined for patients receiving 2 g 5-ASA daily, these changes did not reach statistical significance when compared to placebo-treated patients. On a five point scale (much improved, somewhat improved, unchanged, somewhat worse, much worse) the physician's global assessment mirrored the changes in disease activity index. Patients randomized to receive 4 g 5-ASA tablets were consistently noted as being either much or somewhat improved compared to placebo-treated patients. Side effects were few and minor and 52% (4 g 5-ASA), 42% (2 g 5-ASA) and 37% (placebo) of patients had no complaints. Headache was the most commonly cited adverse reaction for 6.9% (4 g 5-ASA) and 9.4% (2 g 5-ASA) of treated patients but 3.5% of placebo-treated patients also complained of headache. In conclusion in this randomized double-blind, placebo controlled study, patients with active ulcerative colitis randomized to 4 g 5-ASA per day noted improvement in disease activity as measured by disease activity index and physician's global assessment when compared to placebo-treated patients. ln contrast, patients who received 2 g 5-ASA daily did not demonstrate significant differences compared to the placebo group.

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Section: Discussionmentioning

confidence: 99%

A Double-Blind, Placebo Controlled, Multicentre Study of the Efficacy And Safety of 5-Aminosalicylic Acid Tablets in the Treatment of Ulcerative Colitis

Sutherland¹,

Mg²,

Onstad³

et al. 1990

Canadian Journal of Gastroenterology

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“…The findings of only 23% renally eliminated drug, on the other hand, points to a decreased absorption of 5-ASA in patients with UC when comparing with values found in the above-mentioned studies (24, 94, 102, I). These results may imply different pharmacokinetics of 5-ASA in UC-patients compared to healthy subjects with a decreased small bowel absorption or a alternative 5-ASA metabolism related to IBD (1). Contrary to this, it was recently found in comparative studies, that systemic elimination of SR-5-ASA did not differ between CIBD-patients and healthy subjects (80, 95).…”

Section: Vi23 Related Studiesmentioning

confidence: 83%

“…N-acetyl-5-ASA is the main metabolite of 5-ASA but other metabolites and derivatives of 5-ASA have been reported. Some are well-known derivatives, i.e.salicylate and gentisate (36), others are newly identified conjugates (119,120) and oxidative products (1,58). Degradation of 5-ASA by enzymatic cleavage in the faecal bacteria has also, recently, been demonstrated (1 12).…”

Section: Vi433 Concluding Remarksmentioning

confidence: 99%

Untitled

1997

Pharmacology & Toxicology

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“…In fact, several authors have pointed out that the therapeutic activity of drugs used in inflammatory bowel disease in humans, such as sulfasalazine and its therapeutically active metabolite 5-aminosalicylic acid, may be related to suppression of reactive oxygen production at intestinal mucosal level (Craven et al, 1987;Ahnfelt-Ronne et al, 1990). …”

Section: Discussionmentioning

confidence: 99%