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At least 487 records · Page 27Linked to original sources
PubMed1988

Sulfasalazine-induced abnormal sperm penetration assay reversed on changing to 5-aminosalicylic acid enemas.

Sulfasalazine, a drug used in the treatment of inflammatory bowel disease, has been associated with male infertility, an effect attributed to sulfapyridine rather than to 5-aminosalicylic acid (5-ASA), the presumed therapeutically active component of sulfasalazine. Recently, the sperm penetration assay (SPA) has been found to be an accurate method of quantitating male fertilization potential. We report the case of a man with ulcerative colitis in whom infertility and a markedly abnormal SPA were demonstrated while he was taking sulfasalazine. Shortly after discontinuing sulfasalazine and initiating treatment with 5-ASA enemas, his SPA became normal and his wife became pregnant. The SPA is a useful screening test for sulfasalazine-induced male infertility. On the other hand, 5-ASA enemas do not appear to be associated with an abnormal SPA.

Adult↗
PubMed1999

The systemic load and efficient delivery of active 5-aminosalicylic acid in patients with ulcerative colitis on treatment with olsalazine or mesalazine.

BACKGROUND: There have been reports of nephrotoxic reactions in patients with ulcerative colitis treated with 5-aminosalicylic acid (5-ASA) preparations. AIM: To compare the efficacy in delivery of active 5-ASA to the colon and the systemic load as the basis for potential long-term toxicity during treatment with olsalazine or mesalazine in patients with ulcerative colitis in remission. PATIENTS AND METHODS: Fifteen patients with ulcerative colitis were treated with olsalazine or mesalazine, each for 7 days in an open, randomized, crossover design study. 5-ASA and acetyl-5-ASA (Ac-5-ASA) in plasma and urine were measured by high performance liquid chromatography. RESULTS: The plasma concentration of 5-ASA was 1.2 +/- 0.1 micromol/L (mean +/- S.E.M.) for olsalazine and 8.0 +/- 1.9 micromol/L for mesalazine, while the plasma concentration of Ac-5-ASA was 2.8 +/- 0.2 micromol/L for olsalazine and 10.8 +/- 1.6 micromol/L for mesalazine. The amount of 5-ASA excreted in the urine was 68 +/- 30 micromol/24 h for olsalazine and 593 +/- 164 micromol/24 h for mesalazine. The amount of Ac-5-ASA in the urine was 1260 +/- 102 micromol/24 h for olsalazine and 3223 +/- 229 micromol/24 h for mesalazine. The urinary recovery of total 5-ASA plus Ac-5-ASA (as a percentage of the given dose) was 23 +/- 2.1% for olsalazine and 39 +/- 3.6% for mesalazine. The ratio between the plasma concentrations of mesalazine and olsalazine differed significantly both for 5-ASA (5.1) and Ac-5-ASA (3.6); for 5-ASA (9. 9) and Ac-5-ASA (2.6) in urine, and for the urinary recovery of total 5-ASA plus Ac-5-ASA (1.7). Moreover, in the mesalazine group there was a large variation in the individual plasma concentrations of 5-ASA and Ac-5-ASA, with maximal values 5-6-fold higher than that in the olsalazine group. CONCLUSION: The systemic load of active 5-ASA is significantly higher for mesalazine than for olsalazine, when based on the dosages given and when calculated on an equimolar basis. Some of the patients in the mesalazine group showed unexpected high levels of plasma and urinary 5-ASA concentrations, a finding which may have long-term safety implications.

Adult↗
PubMed1992

Calcium alginate beads as core carriers of 5-aminosalicylic acid.

The utilization of calcium alginate beads as core carriers for delayed dissolution followed by burst release as a potential method of intestinal site specific drug delivery was investigated. 5-Aminosalicylic acid was spray-coated on dried calcium alginate beads and then coated with different percentages of enteric coating polymer and/or sustained-release polymer. Beads coated with more than 6% (w/w) methacrylic copolymer plastisized with dibutyl sebacate and triethyl citrate resisted release in 2-hr acid fluid challenge and allowed immediate dissolution upon transfer to simulated intestinal fluid. With 6% (w/w) methacrylic copolymer on top of 4% (w/w) ethylcellulose polymer, the major portion of drug did not release in 2 hr of acid treatment or the next 3 hr of simulated intestinal fluid treatment. This dosage form provides the possibility to deliver drug to the lower intestinal tract with minimal early release, followed by sustained release in the colon.

Alginates↗
PubMed1989

Failure of 5-aminosalicylic acid enemas to improve chronic radiation proctitis.

Radiation proctitis is a well-known complication of abdominal and pelvic radiation. Conventional medical and surgical treatment often is disappointing. 5-Aminosalicylic acid (5-ASA) is the active component in sulfasalazine and is effective in the treatment of distal ulcerative colitis. Four patients with radiation proctitis were treated with 4 g 5-ASA by enema nightly for two to six months. Patients were seen monthly, interviewed, and a sigmoidoscopic exam performed. No change was seen in the degree of mucosal inflammation on follow-up sigmoidoscopic exams. Three patients noted no change in their symptoms of bleeding, pain, or tenesmus. One patient noted initial improvement, but this was not sustained. 5-ASA enemas do not appear to be effective in the treatment of radiation proctitis.

Aminosalicylic Acids↗
PubMed2003

Para-aminosalicylic acid (PAS) desensitization review in a case of multidrug-resistant pulmonary tuberculosis.

SETTING: Tertiary care hospital in the Upper Midwest, United States. OBJECTIVE: Rapid desensitization to para-aminosalicylic acid (PAS) in a patient with previous hypersensitivity reaction and a review of published PAS desensitization protocols. DESIGN: Composition and implementation of a short-course PAS desensitization protocol for a 34-year-old woman with multidrug-resistant (MDR) pulmonary tuberculosis, incorporating published experiences of PAS desensitization over the past 50 years. RESULTS: We composed a protocol and successfully desensitized our patient to PAS (Paser granules). By starting with a low dose (50 mg), then doubling the PAS dose on each successive day, our patient was able to tolerate full dose in 1 week. No steroids were required and no adverse reactions were encountered. Previous published PAS desensitization protocols used starting doses of 10-500 mg, desensitization time ranges from 7 to 54 days and commonly used steroids or corticotropin. CONCLUSION: Rapid desensitization to PAS can be successfully conducted within 1 week without the use of steroids or corticotropin. Given the limited number of drugs available for many patients with MDR-TB, desensitization to PAS is a valid alternative to drug discontinuation for patients with hypersensitivity reactions.

Adult↗
PubMed1986

Steady-state kinetics of 5-aminosalicylic acid and sulfapyridine during sulfasalazine prophylaxis in ulcerative colitis.

Fifteen adult and 19 pediatric outpatients with ulcerative colitis were studied to determine the steady-state kinetics of 5-aminosalicylic acid (5-ASA) released from salazosulfapyridine (SASP). Results of excretion in adults (mean 24-h recovery of 5-ASA, 21% in urine and 57% in feces) were compatible with those of healthy volunteers. Since mean SASP dose/kg body weight (about 50 mg/kg) and compliance (reflected in sulfapyridine recovery) were equal in adults and pediatric patients, the results of the patient groups could be compared. Near-complete azo reduction of SASP occurs in children. Absorption and excretion of 5-ASA and metabolism to acetyl-5-ASA did not differ statistically between pediatric and adult patients. However, the fecal excretion of the drug and its metabolites was significantly lower in young patients, although fecal concentrations were the same. The present results demonstrate that SASP is an excellent sustained-release drug for the delivery of 5-ASA to the lower part of the bowel system and provide a reference for comparison of 5-ASA kinetics after treatment with newer 5-ASA preparations.

Adolescent↗
PubMed1987

Lack of effect of 5-aminosalicylic acid on platelet aggregation and fibrinolytic activity in vivo and in vitro.

We have studied platelet aggregation and fibrinolytic activity in six patients with chronic inflammatory bowel disease treated with 5-aminosalicylic acid (mesalazine). There were no changes in these measurements during normal treatment, i.e. 1.5 g per day with a slow-release formulation, nor after an intravenous dose of 250 mg. Also in vitro tests were negative, in contrast to the inhibition seen with aspirin (acetylsalicylic acid). We conclude that treatment with mesalazine does not constitute a hazard to these patients in regard to prolonged bleeding time caused by an influence on platelet aggregation or fibrinolytic activity.

Adult↗
PubMed1997

Combined therapy with 5-aminosalicylic acid tablets and enemas for maintaining remission in ulcerative colitis: a randomized double-blind study.

OBJECTIVES: To assess the efficacy of a combination of oral and topical 5-aminosalicylic acid (5-ASA) for the maintenance treatment of ulcerative colitis, we undertook a double-blind randomized clinical trial. METHODS: Patients aged 18 to 65 yr (with disease extent greater than proctitis only) were eligible for inclusion in the study if they met the following criteria: (a) history of two or more relapses in the last year; (b) achievement of remission in the last 3 months (with maintenance of remission for at least 1 month). Patients enrolled in the study were randomly assigned to one of the two following 1-yr treatments: (1) combined therapy with 5-ASA tablets 1.6 g/day and 5-ASA enemas 4 g/100 ml twice weekly; (2) oral therapy with 5-ASA tablets 1.6 g/day and placebo enemas/twice weekly. The main end point of the study was the maintenance of remission at 12 months. RESULTS: Upon completion of the study, relapse occurred in 13 of 33 patients in the combined treatment group versus 23 of 36 patients in the oral treatment group (39 vs 69%; p = 0.036). No significant side effects related to treatment were observed in either group. A simplified pharmacoeconomic analysis shows that this form of combined treatment can have a favorable cost-effectiveness ratio. CONCLUSIONS: Our results indicate that 5-ASA given daily by oral route and intermittently by topical route can be more effective than oral therapy alone. This form of combination treatment can be appropriate for patients at high risk of relapse.

Administration, Oral↗
PubMedDate not supplied

Systemic levels of free 5-aminosalicylic acid depend on the nature of the 5-aminosalicyclic acid derivative and not on disease activity or extent in patients with inflammatory bowel disease.

INTRODUCTION: Several new derivatives of sulphasalazine that make use of its active moiety, 5-aminosalicylic acid (5-ASA), have been introduced for the treatment of inflammatory bowel disease (IBD). In rats short term intravenous administration of 5-ASA has been associated with nephrotoxicity. A number of cases of nephrotoxicity have been reported recently in IBD patients taking oral maintenance treatment with 5-ASA compounds. OBJECTIVE: To study the urinary and serum levels of acetylated 5-ASA (Ac-5-ASA) and the unacetylated 5-ASA (5-ASA) in patients with IBD maintained on sulphasalazine, olsalazine and mesalazine (pH dependent release form). We also sought correlation between levels of 5-ASA, clinical disease activity and extent of disease. METHODS: We studied 79 patients (male, n = 30; female, n = 49) with established IBD [ulcerative colitis (UC), n = 48; Crohn's disease (CD), n = 31], 72 maintained on 5-ASA compounds (sulphasalazine = 27; olsalazine = 28; mesalazine = 17) and 7 patients were receiving no medication. Urinary and serum analysis of 5-ASA was performed by high performance liquid chromatography (HPLC). Clinical disease activity was quantified using simple index of Harvey and Bradshaw. RESULTS: Patients receiving mesalazine had significantly higher levels of serum free 5-ASA compared to those who were receiving olsalazine and sulphasalazine (mesalazine mean +/- SEM; range; 2.84 +/- 1.21 (0.00-16.00) vs olsalazine 0.45 +/- 0.18 (0.00-16.20); mumol/L; p < 0.04; sulphasalazine 0.37 +/- 0.25 (0.00-3.74); p < 0.03). Similarly levels of urinary free 5-ASA were significantly higher in patients maintained on mesalazine compared to those on olsalazine or sulphasalazine (mesalazine 219 +/- 80.43 (0.00-1050) vs olsalazine 33.3 +/- 17.23 (0.00-317) mumol/L; p < 0.01; and sulphasalazine 15 +/- 8.86 (0.00-192); p < 0.05). However, no significant difference was observed in the levels of urinary free 5-ASA between olsalazine and sulphasalazine. No significant difference was observed in the levels of free-5-ASA in UC patients with left sided disease and those with extensive disease. Furthermore, no significant difference was observed in the levels of serum and urinary 5-ASA in CD patients with ileo-colic disease and colonic disease. Urinary and serum free-5-ASA did not correlate with the clinical disease activity. CONCLUSION: Systemic absorption of 5-ASA from sulphasalazine and olsalazine is relatively low. However, pH-dependent mesalazine formulations may release their contents rapidly in the small intestine and proximal colon resulting in higher plasma and urinary concentrations of free 5-ASA. The effects of free 5-ASA on renal function in the human require further evaluation.

Adolescent↗
PubMed1999

5-aminosalicylic acid inhibits iNOS transcription in human intestinal epithelial cells.

The mechanism by which 5-aminosalicylic acid (5-ASA) reduces mucosal injury in colitis is undefined. In murine cells, 5-ASA modulates the expression of the inducible nitric oxide (NO) synthase, a potential mediator of colitic injury, but its effect on the human isoform is unknown. Given the lack of conserved regulation of iNOS expression in rodent and human systems, we sought to test the effect of 5-ASA on the expression of human iNOS in cultured enterocytes. Transformed human intestinal epithelial cells, DLD-1 and Caco-2BBe, were stimulated by IL-1beta and IFN-gamma and analyzed for iNOS upregulation and NO production in the presence of various aminosalicylates. 5-ASA, but not 4-ASA, dose-dependently inhibited NO production by both cell lines [IC50 (mM) DLD-1 =4.5, Caco-2BBe =2. 5]. 5-ASA also inhibited the expression of iNOS protein and mRNA and blocked cytokine-induced transcriptional upregulation of the iNOS gene. 5-ASA (1-5 mM) had no effect on cytokine-induced nuclear translocation of NF-kappaB or expression of IRF-1, transactivating factors which regulates the human iNOS enhancer. We conclude that 5-ASA inhibits iNOS expression and NO production at therapeutically relevant concentrations. The inhibition occurs at the level of transcriptional activation and is independent of IRF-1 and NF-kappaB. Since NO is an important final effector of mucosal injury in inflammatory bowel disease, these findings may have implications for the clinical efficacy of 5-ASA.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1995

Pharmacokinetics of 5-aminosalicylic acid from controlled-release capsules in man.

One gram single dose of Pentasa controlled-release capsules was administered to 24 healthy volunteers under fasting condition. Mean plasma 5-aminosalicylic acid (5-ASA) and acetyl 5-ASA concentrations peaked at 0.53 microgram.ml-1 and 1.33 micrograms.ml-1 from 3 to 4 hours following dosing, respectively. The half-lives of both compounds could not be determined as absorption of 5-ASA was continuous throughout the gastrointestinal tract. An average of 29.4% (CV: 27%) of the dose was excreted in the urine primarily as acetyl 5-ASA. Up to 91.1% of the dose was released from the capsules. Forty percent of the dose (CV: 40%) was eliminated in the feces, with 8.9% of the dose remained as formulation bounded 5-ASA, indicating that controlled-release capsules continue to release drug throughout the GI tract. 5-ASA contributed 46.7% of the salicylates eliminated in the feces and acetyl 5-ASA accounted for the balance. Controlled-release capsules produced three times more total salicylates and 10 times more total and free 5-ASA in the feces than did 5-ASA suspension. Thus, while lower systemic levels of salicylates were absorbed, greater therapeutic quantities of 5-ASA were available in the bowel.

Adult↗
PubMed1985

The value of 5-aminosalicylic acid in inflammatory bowel disease for patients intolerant or allergic to sulphasalazine.

The use of sulphasalazine in inflammatory bowel disease is often limited by intolerance or allergy. In previous studies 5-aminosalicylic acid (5ASA), the active ingredient of sulphasalazine, coated with an acrylic resin, has been shown to be as effective as sulphasalazine in maintaining remission. In this study coated 5ASA was given to 37 patients intolerant or allergic to sulphasalazine. Thirty-three patients have tolerated 5ASA satisfactorily, and most experienced improved control of their disease. Four patients reported similar side effects with sulphasalazine and 5ASA.

Adult↗
PubMed1989

Assessment of salicylate derivatives for potential use in ulcerative colitis: proposal for a new action of 5-aminosalicylic acid?

The therapeutic efficacy of salicylate drugs for ulcerative colitis in vivo is related to the capacity of each drug to suppress fatty acid oxidation in colonocytes in vitro. The suppression index of fatty acid oxidation (SIFO) was assessed with 17 salicylate drugs of either known or unknown therapeutic efficacy. The high SIFO value of 5-aminosalicylic acid (5-ASA) was reduced to zero when the amino group was replaced with a methyl, nitro, hydroxyl or bromine group. The SIFO of 3-ASA was dose-related and 2- to 3-fold greater than the SIFO of 5-ASA. The antioxidants methyl- or propyl-4-hydroxybenzoate have a high SIFO, but show a 'toxic' action towards colonocytes not observed with 3-ASA, 4-ASA or 5-ASA. A new cellular action proposed for 5-ASA is that acetylation of the amino group of 5-ASA in colonocytes releases free CoA countering sequestration of CoA observed in epithelial cells during active colitis.

Aminosalicylic Acids↗