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At least 19 recordsLinked to original sources
PubMed1984

A double-blind clinical trial to compare the effects of 4-aminosalicylic acid to 5-aminosalicylic acid in topical treatment of ulcerative colitis.

5-Aminosalicylic acid (5-ASA) is the active component of Salazopyrin and induces a prompt and excellent improvement, when administered as high dosage enema, in patients suffering from active ulcerative colitis. However, the high instability of this metabolite makes its large use difficult. We aimed at finding a more stable preparation and therefore wondered whether another similar molecule, i.e. 4-aminosalicylic acid (4-ASA, generally known as p-aminosalicylic acid, PAS), which differs from 5-ASA only for the position of the amino group, might be a valid alternative. Therefore, 4-ASA at 2 g dosage, administered as rectal enema, was compared to an equivalent preparation of 5-ASA. We carried out a double-blind therapeutical trial, in which 63 patients, similarly matched for age, sex and extent of disease, took part. The analysis of the final results showed that in the 5-ASA group, 26 (81%) out of 32 patients improved clinically, 25 (78%) sigmoidoscopically and 15 (46%) histologically. In the group of the 31 patients treated with 4-ASA, 24 (77%) improved clinically, 24 (77%) sigmoidoscopically and 13 (41%) histologically. Since no difference was registered between the two types of treatment (p = 0.141, X2 test), 4-ASA could be a possible form of treatment for active ulcerative colitis.

Aminosalicylic Acid↗
PubMed1994

Oral 4-aminosalicylic acid versus 5-aminosalicylic acid slow release tablets. Double blind, controlled pilot study in the maintenance treatment of Crohn's ileocolitis.

4-Aminosalicylic acid (4-ASA) has been suggested as an effective treatment for both active and quiescent ulcerative colitis. 5-Aminosalicylic acid (5-ASA) is well accepted for the maintenance treatment of inactive ulcerative colitis. Moreover, recent studies suggest that 5-ASA may also be effective in maintaining remission in Crohn's colitis. As treatment with 4-ASA may result in less side effects, the efficacy of a one year's maintenance treatment with oral 4-ASA (1.5 g/d, slow release tablets, n = 19) and oral 5-ASA (1.5 g/d, slow release tablets, n = 21) was compared in a double blind, randomised trial in patients with quiescent Crohn's ileocolitis. Patients with ileocolonic or colonic involvement were enrolled if in stable remission for more than two months but less than one year. Baseline demography and clinical severity were similar in both groups. Total colonoscopy and ileoscopy were performed at enrollment and at the end of the study. After one year seven of 19 patients receiving 4-ASA (36%) and 8 of 21 receiving 5-ASA (38%) had developed a clinical relapse, as defined by a rise in the Crohn's disease activity index (CDAI) of more than 100 points to values higher than 150. The relapse rates between the 4-ASA and the 5-ASA groups were not statistically different although no comparison with the spontaneous relapse rate in a placebo group could be made. Clinical relapse was accompanied by a statistically significant rise in serum concentrations of soluble interleukin 2 receptor and by an increased percentage of activated peripheral blood T cells. There were no statistical differences between the 4-ASA and the 5-ASA groups regarding the height of rise in CDAI or of soluble interleukin 2 receptor concentrations during relapse, thus showing a similar severity relapsed disease activity. In conclusion, 4-ASA maybe as effective as 5-ASA in the maintenance treatment of quiescent Crohn's disease and there were no differences in the severity of relapse between both treatment groups.

Administration, Oral↗
PubMed1995

Simultaneous determination of 5-aminosalicylic acid, acetyl-5-aminosalicylic acid and 2,5-dihydroxybenzoic acid in endoscopic intestinal biopsy samples in humans by high-performance liquid chromatography with electrochemical detection.

A high-performance liquid chromatographic method for the simultaneous determination of 5-aminosalicylic acid (5-ASA), acetyl-5-aminosalicylic acid (Ac-5-ASA) and 2,5-dihydroxybenzoic acid (5-HSA) in human endoscopic intestinal biopsy with electrochemical detection has been developed and validated. A liquid-liquid extraction procedure was used to isolate these drugs from the biological material prior to analysis. The compounds were separated on an Erbasil S reversed-phase column using methanol-critic acid-sodium hydrogenphosphate-heptane-sulfonic acid-disodium ethylenediaminetetraacetate (pH 3) as mobile phase. The method was linear from 1.0 to 300 ng ml-1 for 5-ASA, from 10 to 1000 ng ml-1 for Ac-5ASA and from 0.1 to 10 ng m-1 for 5-HSA. The limit of detection for 5-ASA and for Ac-5-ASA was 1 ng ml-1 and that for 5-HSA was 0.1 ng ml-1. This procedure is suitable for pharmacological and clinical studies of 5-ASA.

Aminosalicylic Acids↗
PubMed1984

Soybean lipoxygenase inhibition: studies with the sulphasalazine metabolites N-acetylaminosalicylic acid, 5-aminosalicylic acid and sulphapyridine.

Soybean lipoxygenase inhibition has been proposed as an in vitro biochemical model for the antiinflammatory action of certain drugs used in the treatment of ulcerative colitis. In an extension of a recent study which showed that therapeutically active compounds, such as sulphasalazine and its colonic metabolite 5-aminosalicylic acid were soybean lipoxygenase inhibitors, it has now been shown that N-acetylaminosalicylic acid, the principal metabolite of 5-aminosalicylic acid, also inhibits soybean lipoxygenase in a dose dependent and noncompetitive manner (Ki 3.0 X 10(-8) M, IC50 250 microM). Sulphapyridine, the other major metabolite of sulphasalazine, which has been demonstrated to be inactive in the treatment of ulcerative colitis, did not inhibit the lipoxygenase activity. The findings further support the hypothesis that only the therapeutically active compounds are soybean lipoxygenase inhibitors.

Aminosalicylic Acids↗
PubMed1988

Double-blind comparison of 5-aminosalicylic acid and acetyl-5-aminosalicylic acid suppositories in patients with idiopathic proctitis.

Suppositories containing 300 mg 5-aminosalicylic acid (1.96 mmol) or 425 mg acetyl-5-aminosalicylic acid (1.96 mmol) were used in 40 patients with idiopathic proctitis to determine the efficacy of acetyl-5-aminosalicylic acid in treating this bowel inflammation. Each patient was treated with 5-aminosalicylic acid or acetyl-5-aminosalicylic acid suppositories twice daily for 4 weeks in a double-blind trial. Four patients were included twice in the trial. The second time they were treated with the alternative regimen. Six patients in the acetyl-5-aminosalicylic acid group did not complete the trial, four of them because of diarrhoea. Complete clinical remission with normal rectal mucosa on sigmoidoscopy was achieved in 10 out of 18 patients on 5-aminosalicylic acid and in only two out of 15 in the acetyl-5-aminosalicylic acid group (P = 0.03). A favourable histological improvement was demonstrated with 5-aminosalicylic acid suppositories, but the difference with acetyl-5-aminosalicylic acid was not significant (P = 0.059). Three of the four patients who received both drugs recovered with 5-aminosalicylic acid; in none of them was acetyl-5-aminosalicylic acid effective. The results from this study and from previous investigations show that acetyl-5-aminosalicylic acid is not superior to placebo.

Adult↗
PubMed1994

Disposition of 5-aminosalicylic acid and N-acetyl-5-aminosalicylic acid in fetal and maternal body fluids during treatment with different 5-aminosalicylic acid preparations.

STUDY OBJECTIVE: To determine the concentration of 5-aminosalicylic acid (5-ASA) and the metabolite N-acetyl-5-aminosalicylic acid (Ac-5-ASA) in the maternal and fetal plasma at delivery and in the maternal milk post partum. DESIGN AND STUDY SUBJECTS: Pregnant and lactating women with chronic inflammatory bowel disease, treated with different pure 5-ASA preparations participated in the study. At delivery, samples of fetal and maternal plasma were obtained from nine women. The excretion in milk was measured and the time of medicine intake was registered during a 24 h period 2-4 weeks after delivery in 13 women. RESULTS: Concentrations of 5-ASA in the fetal plasma were lower than in maternal plasma. Plasma concentrations of Ac-5-ASA were detectable in all the nine samples and similar levels in the mother and the fetus were found at the time of delivery. In three women 5-ASA was detected in the milk in low concentrations. The concentration of Ac-5-ASA in the milk varied considerably during the 24 h collection period, and also between individuals; its concentration tended to be higher than in the plasma. No time relation between medicine intake and maximal concentration in the milk was found. Based on the maximal Ac-5-ASA concentration and a milk intake of one liter/daily, the newborn receives less than 15 mg Ac-5-ASA daily. CONCLUSION: The study indicates that treatment with pure 5-ASA preparations in conventional doses is without risk to the fetus and the newborn.

Aminosalicylic Acids↗
PubMed2002

Chemoprevention of N-methylnitrosourea-induced colon carcinogenesis by ursodeoxycholic acid-5-aminosalicylic acid conjugate in F344 rats.

Bile acids enhance colon carcinogenesis in animal models, whereas ursodeoxycholic acid (UDCA) suppresses it. Nonsteroid anti-inflammatory drugs prevent colon cancer development in animals and humans. The aim of the present study was to explore the inhibitory effect of UDCA conjugate with 5-aminosalicylic acid (5-ASA), UDCA-5-ASA conjugate (UDCA-5-ASA), against colon carcinogenesis in rats. One-hundred-and-twenty-nine 7-week-old F344 rats received an intrarectal instillation of 2 mg of N-methylnitrosourea 3 times a week for 3 weeks, and were fed a 0% (control), 0.11% or 0.02% UDCA-5-ASA-, 0.08% UDCA- or 0.03% 5-ASA-supplemented diet for the next 27 weeks. The test diets contained an equimolar amount of a test agent, 2.0 mmol/kg diet, except for the 0.02% UDCA-5-ASA diet. The tumor incidence and the mean number of tumors/rat at week 30 were significantly lower and smaller in the UDCA-5-ASA diet groups, 48% and 0.7 in both, and marginally lower in the UDCA and 5-ASA diet groups, 56% and 0.9, and 64% and 0.8, compared to the control group, 83% and 1.3. All the tumors were polypoid in shape, and most of them were differentiated adenocarcinomas restricted to the mucosa or submucosa. An analysis by HPLC for bile acids and 5-ASA in the feces and serum collected at week 30 showed that one-half of ingested UDCA-5-ASA was cleaved into UDCA and 5-ASA in the colon. Thus, the two moieties may have independently affected the promotion stage of carcinogenesis.

Animals↗
PubMed2001

Colon-specific prodrugs of 5-aminosalicylic acid: synthesis and in vitro/in vivo properties of acidic amino acid derivatives of 5-aminosalicylic acid.

5-aminosalicyl-L-aspartic acid (5-ASA-Asp) and 5-aminosalicyl-L-glutamic acid (5-ASA-Glu) were synthesized and their properties as colon-specific prodrugs of 5-aminosalicylic acid (5-ASA) were investigated employing rats as test animals. Incubation of 5-ASA-Asp and 5-ASA-Glu with the homogenates of tissue and contents of stomach or small intestine released no 5-ASA, indicating that they were stable in this condition. Incubation of 5-ASA-Asp with the cecal contents released 5-ASA 37%, whereas 5-ASA-Glu released only 8% of the dose in 16 h. Plasma concentration of 5-ASA-Asp after intravenous administration decreased rapidly and became undetectable in 60 min. No 5-ASA was detected in the blood, which indicated 5-ASA-Asp was stable in the plasma. After oral administration of 5-ASA-Asp, concentration of 5-ASA, its metabolite N-acetyl-5-ASA, and 5-ASA-Asp in the plasma, feces, and urine was determined. In the plasma, 5-ASA-Asp was not detected and the concentration of 5-ASA or N-acetyl-5-ASA was very low. About 33% of the administered dose was recovered as 5-ASA and N-acetyl-5-ASA and 43% as 5-ASA-Asp from feces, and 20% as 5-ASA and N-acetyl-5-ASA and 1% as 5-ASA-Asp from urine in 24 h. These results suggested that most of 5-ASA-Asp was delivered to the large intestine and about half of the administered dose was activated to liberate 5-ASA. After oral administration of free 5-ASA, fecal recovery was only 7% of the dose in 24 h and more than 80% was recovered from urine. Comparing 5-ASA-Asp and free 5-ASA, the amount of 5-ASA available in the large intestine was much larger, while the amount of 5-ASA in urine, which might be related to the systemic toxicity of 5-ASA, was much lower by the administration of 5-ASA-Asp than free 5-ASA.

Administration, Oral↗
PubMed1992

The effects of 5-aminosalicylic acid and acetyl-5-aminosalicylic acid on lipid peroxidation in erythrocytes and prostaglandin production by mononuclear cells.

In parallel studies, the effects of 5-aminosalicylic acid (5-ASA) and acetyl-5-aminosalicylic acid (acetyl-5-ASA) on peroxidation of red-cell membrane lipids and production of prostaglandins by peripheral blood mononuclear cells were assessed. 5-ASA at concentrations of 10(-5), 10(-4) and 10(-3) M significantly inhibited erythrocyte lipid peroxidation, measured as malondialdehyde production, by 20%, 56% and 63%, respectively, (P < 0.05, P < 0.002, P < 0.001, respectively) while acetyl-5-ASA had no effect. 10(-5) and 10(-4) M 5-ASA significantly increased production by stimulated peripheral blood mononuclear cells of PGE2 (by 31% and 30%, P < 0.01, P < 0.05, respectively) and PGF2 alpha (by 30% and 25%, P < 0.05, P < 0.01, respectively). 10(-4) M 5-ASA also significantly stimulated prostacyclin production measured as 6KF1 alpha by 10% (P < 0.05). At 10(-3) M 5-ASA there were significant falls in 6KF1 alpha (by 37%) PGE2 (by 45%) and PGF2 alpha (by 47%) (P < 0.01, P < 0.001, P < 0.001, respectively) although this was accompanied by a decrease in cell viability. Acetyl-5-ASA had little effect upon prostaglandin production. 5-ASA scavenges free radicals and stimulates production of cytoprotective prostaglandins.

Aminosalicylic Acids↗
PubMed2003

Synthesis, characterization and in vitro release of 5-aminosalicylic acid and 5-acetyl aminosalicylic acid of polyanhydride--P(CBFAS).

A novel polyanhydride, poly[(5-carboxybutyl formamide)-2-acetyl salicylic anhydride] (P(CBFAS)), with 5-aminosalicylic acid (5-ASA) incorporated into the polymer backbone was synthesized and characterized by infrared, (1)H-nuclear magnetic resonance, differential scanning calorimetry, vapor pressure osmometry, etc. The polyanhydride was subjected to degradation and simultaneously released 5-ASA and its derivative 5-acetyl aminosalicylic acid (5-acetyl ASA) in vitro under various conditions. The factors influencing the release profiles of 5-ASA and 5-acetyl ASA, including polymer molecular weights, pH value, enzyme and rat gastrointestinal contents, were examined. The results showed that the release rate of 5-ASA and 5-acetyl ASA increases with increasing pH value and with decreasing molecular weights. In PBS (pH 8.0, 37 degrees C) total ASA released was 8.0% for P(CBFAS)(1) (Mn 10770) in 13 h, but only 1.1 and 2.6% at pH 2.0 and 6.5, respectively. Enzymes including pepsin and trypsin, as well as rat gastric and jejunum contents had little effect on the release rate of 5-ASA and 5-acetyl ASA at pH 2.0 and 6.5 (less than 4% in 13 h). However, the release rate of 5-ASA and 5-acetyl ASA was much fast in PBS(pH 8.0) containing 5% of cecal contents, the total ASA released was 13.6% for the polymer in 13 h. Considering the high drug loading of the polymer (50.2% of 5-ASA moieties in the backbones) and the degradation characters, it is possible to reach high local concentration of 5-ASA in the colon site via oral administration. Therefore, P(CBFAS) may be potentially useful in the colon specific delivery of 5-ASA.

Aminosalicylic Acids↗
PubMed1988

4-Aminosalicylic acid, in contrast to 5-aminosalicylic acid, has no effect on arachidonic acid metabolism in human neutrophils, or on the free radical 1,1-diphenyl-2-picrylhydrazyl.

5-Aminosalicylic acid seems to be the active moiety of sulfasalazine in the treatment of chronic inflammatory bowel disease. Even if the precise mode of action is obscure, it is assumed that two of the main mechanisms are inhibitory effects on the lipoxygenation of arachidonic acid and interaction with free radicals. As 4-aminosalicylic acid has been claimed to be beneficial in the topical treatment of ulcerative colitis, it was tested whether this drug possesses any influence on the 5-lipoxygenase activity in human neutrophils in vitro or whether it acts as a radical scavenger. The change of the amino residue from carbon-5 to carbon-4 abolished the effect in the two systems tested. The reported clinical observations on 4-aminosalicylic acid in the treatment of chronic inflammatory bowel disease remain to be confirmed and cannot be explained by interference with arachidonic acid metabolism or free oxygen radicals.

Aminosalicylic Acid↗
PubMed1994

Radical-derived oxidation products of 5-aminosalicylic acid and N-acetyl-5-aminosalicylic acid.

5-Aminosalicylic acid is an agent effective in the treatment of chronic inflammatory bowel diseases. Its ability to scavenge radicals is considered to be a major factor responsible for its therapeutic efficacy. In this study oxidation products of aminosalicylates with hydroxyl radicals were produced. The compounds that could be discovered by gas chromatographic-mass spectrometric analysis originate from a 1,4-benzoquinone monoimine intermediate which subsequently undergoes multiple reactions such as hydrolysis, reductive 1,4-Michael addition, reoxidation and decarboxylation. Some of these products could represent metabolites formed under in vivo conditions and thus provide a tool for screening biological material from subjects under different clinical conditions.

Aminosalicylic Acids↗
PubMed1988

Disposition of 5-aminosalicylic acid by 5-aminosalicylic acid-delivering compounds.

The disposition of 5-aminosalicylic acid (5-ASA) from 5-ASA-delivering drugs was studied in eight healthy volunteers. Time-related urinary excretion and faecal excretion of 5-ASA and acetyl-5-ASA were measured after a single oral dose of the azo compounds sulphasalazine and olsalazine, of the slow-release compounds Pentasa, Asacol, and Salofalk, and of plain 5-ASA. Plain 5-ASA was rapidly excreted into urine and had a low faecal recovery, indicating fast absorption proximally in the intestine and little availability to the colon. After ingestion of both azo compounds and slow-release compounds, urinary excretion of 5-ASA was markedly delayed and reduced, and faecal excretion was enhanced. At all points of time there was a significant but not very marked difference in urinary excretion of 5-ASA after ingestion of the azo compounds and the slow-release compounds, in favour of the azo compounds. A significantly larger proportion of the ingested 5-ASA, moreover, was excreted in faeces after intake of azo compounds as compared with slow-release compounds.

Adult↗
PubMed1991

High-performance liquid chromatographic assay for the determination of 5-aminosalicylic acid and acetyl-5-aminosalicylic acid concentrations in endoscopic intestinal biopsy in humans.

A high-performance liquid chromatographic method for the simultaneous determination of 5-amino-salicylic acid (5-ASA) and N-acetyl-5-ASA (Ac-5-ASA) concentrations in endoscopic mucosal biopsy homogenates is presented. The mean recoveries of 5-ASA and Ac-5-ASA from spiked blank biopsy homogenates ranged from 95.9 to 120% and from 92.5 to 100%, respectively. The coefficients of variation for 5-ASA and Ac-5-ASA were 0.7-8.6% and 1.4-12.9%, respectively. This method is useful for direct determination of topical availability of 5-ASA and Ac-5-ASA and probably an accurate parameter of drug bioavailability.

Aminosalicylic Acids↗