Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021390 (inflammatory bowel disease)
 23,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An Eudragit-L coated oral 5-aminosalicylic acid (5-ASA; mesalazine) product (Mesasal), has been formulated to deliver 5-ASA to the distal small intestine and colon for the treatment of inflammatory bowel disease. The purpose of this study was to compare the pharmacokinetic profile of this product to sulphasalazine (SASP; Salazopyrin) and to assess the pharmacokinetics of a suppository 5-ASA dosage form. Twelve healthy volunteers randomly received four single doses of 5-ASA delivering formulations not less than 1 week apart. (a) Mesasal tablets, 2 x 250 mg, fasting; (b) Mesasal tablets, 2 x 250 mg, fed; (c) Salazopyrin tablets, 3 x 500 mg (corresponding to 576 mg 5-ASA), fasting; and (d) Mesasal suppository, 1 x 500 mg, fasting. Plasma 5-ASA and acetyl-5-ASA (Ac-5-ASA) concentrations were followed for 48 h and urine and faecal concentrations for 72 h. Mesasal tablets (fasting) produced a greater area under the concentration-time curve (AUC), peak and time to peak for both plasma 5-ASA and Ac-5-ASA than Salazopyrin. Median urinary recovery values were 21.7% for Salazopyrin and 35.5% for Mesasal (fasting) (P less than 0.01). This means that the systemic absorption was higher after Mesasal than after Salazopyrin. The total faecal recovery values were 38.3 and 26.5%, respectively (NS). Except for a delay of 1.5-.3 h in the time to peak of 5-ASA and Ac-5-ASA plasma levels, the pharmacokinetics of Mesasal tablets were essentially the same in fasting or fed subjects. Suppository administration of 5-ASA resulted in a low median urinary recovery of 10.8%.
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PMID:Pharmacokinetics of a 5-aminosalicylic acid enteric-coated tablet and suppository dosage form. 251 47

Sulfasalazine (SASP) is frequently used in the treatment of chronic inflammatory bowel disease (IBD), particularly colitis. Because the drug poses a theoretical risk for renal tubular damage, 26 patients, 8-18 years of age, with Crohn's ileocolitis were studied. Thirteen children were receiving SASP while 13 served as disease controls. Renal tubular function was assessed by measurement of urinary beta 2-microglobulin and n-acetylglucosaminidase activity. No abnormalities were found on routine measurement of renal function. Similarly, urinary beta 2-microglobulin and n-acetylglucosaminidase activities were within normal limits for patients receiving SASP, as well as for disease controls. Although there is a theoretical risk for renal tubular damage from the prolonged use of SASP, this study would suggest that IBD patients receiving the drug are at no greater risk for renal injury than their counterparts not receiving the medication.
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PMID:Sulfasalazine and renal tubular function: lack of an effect. 285 19

The effects of sulphasalazine (SASP), azodisal sodium (ADS), and their metabolites were tested in vitro on aerobic and anaerobic faecal bacterial strains. Sulphapyridine (SP) had a mild to moderate effect on Escherichia coli and Streptococcus faecalis. SASP also had a growth-inhibitory effect on Strep. faecalis. The other substances had no effect on the aerobic strains. SASP, SP, 5-aminosalicylic acid, and, to a certain extent, N-acetyl-5-aminosalicylic acid exerted a growth-inhibitory effect on the anaerobic strains. Of special interest was the inhibitory effect on Clostridium difficile strains. In recent years the possibility that overgrowth of Cl. difficile could cause flare-ups of inflammatory bowel disease has been discussed. Some studies suggested that SASP treatment could predispose to Cl. difficile superinfection, whereas others found SASP more probable to exert a prophylactic effect. Our findings support the theory that SASP treatment reduces rather than promotes the risk of Cl. difficile superinfection.
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PMID:In vitro effects of sulphasalazine, azodisal sodium, and their metabolites on Clostridium difficile and some other faecal bacteria. 286 92

Sulphasalazine (SASP), used in the treatment of inflammatory bowel disease, is split into sulphapyridine (SP) and 5-aminosalicylic acid (5-ASA) in the colon. Lower plasma levels of SASP and 5-ASA as compared to those of SP may be due to different absorption rates from the colon because of different pK values and pH dependent lipid-water partition coefficients. In this study we determined the pK values of 5-ASA and its major metabolite, N-acetyl amino-salicylic acid (AcASA), by 13C-NMR spectroscopy and compared the pH dependent apparent benzene-water partition coefficients (Papp) of SASP, SP and 5-ASA with respect to their different plasma levels. The COOH group of 5-ASA had a pK value of 3.0, the -NH3+ group had 6.0, the -OH group 13.9; the -COOH group of AcASA had 2.7 and the -OH group 12.9; The Papp of SASP (0.042 +/- 0.004) and 5-ASA (0.059 +/- 0.01) were significantly lower than that of SP (0.092 +/- 0.03) (at pH 5.5).
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PMID:Determination of the pK values of 5-aminosalicylic acid and N-acetylaminosalicylic acid and comparison of the pH dependent lipid-water partition coefficients of sulphasalazine and its metabolites. 286 70

Assessment of the nature, location and extent of the disease, disease activity and the intestinal and extraintestinal complications and manifestations is an essential prerequisite in the treatment of inflammatory bowel disease. Corticosteroids, sulfasalazine (SASP) and rectal administration of 5-aminosalicylic acid (5-ASA) are effective in the treatment of ulcerative colitis. Oral 5-ASA in the form of a slow-release preparation is probably also effective. Rectal SASP or 5-ASA in addition to corticosteroids is indicated in distal colitis. In severe pancolitis oral or intravenous corticosteroids are required, whilst in less severe forms SASP or 5-ASA can be used. However, the safety of 5-ASA over longer treatment periods has yet to be verified. Surgery is indicated in colitis refractory to maximal treatment over several months. Apart from parenteral or enteral nutrition, treatment with prednisolone is effective in acute exacerbations of Crohn's disease. SASP is possibly effective in colonic disease. The role of 5-ASA has yet to be defined. A prednisolone-induced remission can be maintained by means of low doses of prednisolone. SASP is probably not effective, whilst with 5-ASA conclusive data are missing. Metronidazole and azathioprin are considered to be reserve drugs and can be used in the treatment of fistulae or in order to cut down the dosage of prednisolone during remission. Substitution with vitamins and trace elements is necessary in a large number of patients with Crohn's disease.
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PMID:[Drug therapy of chronic inflammatory intestinal diseases--current status of 5-aminosalicylic acid]. 288 Apr 25

1. Prostaglandin (PG) E2 and F2 alpha synthesis in vitro by human rectal mucosa was significantly greater in patients with Inflammatory Bowel Disease (IBD) than in controls. 2. The addition of 250 microM sulphasalazine (SASP) significantly increased synthesis by rectal mucosa from patients with IBD, (ulcerative colitis and Crohn's disease) and controls after 1 h of incubation in Krebs' solution at 37 degrees C. 3. Flurbiprofen, indomethacin, sodium salicylate and 5-aminosalicylic acid decreased PGE2 and F2 alpha synthesis. 4. Sodium carbenoxolone decreased PGF2 alpha synthesis but had no effect on PGE2. Disodium cromoglycate, sulphapyridine, salicylazosulphadimidine and methylsulphasalazine had no effect on PG synthesis. 5. The data show marked variations in effect on PG synthesis in vitro of substances that have been investigated clinically for their actions on IBD.
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PMID:Inflammatory bowel disease: the in vitro effect of sulphasalazine and other agents on prostaglandin synthesis by human rectal mucosa. 289 90

Benzalazine (salicylazobenzoic acid, SAB), a 5-azo derivative of 5-aminosalicylic acid, has been designed as a new therapeutic agent for the treatment of inflammatory bowel disease which might lack the frequent side effects caused by the sulfapyridine moiety of the sulfasalazine molecule (SASP). Here, we report on a prospective, randomized, double-blind comparison of SAB and SASP in patients with an acute relapse of ulcerative colitis. 43 patients with an acute relapse of ulcerative colitis proven by the pertinent endoscopic-macroscopic and histologic criteria were randomized to receive a 6-week course of either 1 g SASP (n = 21) or the equivalent dose of 0.72 g SAB (n = 22) three times a day. Both groups were comparable with respect to demographic data, previous duration and extension of the disease as well as clinical, endoscopic and histologic severity of the relapse. 1 patient on SASP had to be removed from the study due to side effects, while 3 patients on SAB were removed due to rapid worsening of the disease requiring either surgery (1 patient with toxic megacolon) or additional steroid treatment (2 patients). 2 SAB patients were lost to follow-up after substantial improvement had been observed within the first 3 weeks of treatment. In the remaining patients (20 SASP, 17 SAB), stool frequency, stool consistency and macroscopic appearance as well as histology of the diseased mucosa were improved within 6 weeks, with no significant difference between the two groups with respect to any of the parameters recorded. Side effects were recorded in 5 patients on SASP (3 with nausea, 1 with pruritus and 1 with a generalized exanthema) and in 3 patients on SAB (all nausea and vomiting; difference not statistically significant). We conclude that SAB and SASP in equivalent doses are of similar efficacy in the treatment of active ulcerative colitis.
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PMID:Prospective, randomized, double-blind comparison of benzalazine and sulfasalazine in the treatment of active ulcerative colitis. 290 88

Sulfasalazine (SASP) has been used for many years as a disease-modifying agent in inflammatory bowel disease and in rheumatoid arthritis. However, its mode of action is not entirely clear. Evidence has been accumulated which indicates that its efficacy is due to an immunomodulatory effect. In the present communication, we report that SASP has an immunomodulatory capacity in an experimental rat cardiac allograft model. A combination of 100 mg/kg per day of SASP given orally until rejection and 10 mg/kg per day of cyclosporine A (CyA) given orally for 10 days resulted in a significantly increased graft survival time as compared to that in animals given CyA alone.
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PMID:The enhancing effect of cyclosporine A and sulfasalazine on the prevention of rejection in rat cardiac allografts. 290 20

SASP, the drug most widely used for the treatment of Crohn's disease and ulcerative colitis, is a competitive inhibitor of intestinal folate metabolism and transport. Some of the therapeutic effects of the drug could be related to antifolate actions on lymphocytes, which predominate in the inflammatory reaction in inflammatory bowel diseases. Experiments were designed to examine the effect of SASP on folate-dependent systems in cultured lymphocytes. In rat spleen lymphocytes, THF-dependent conversion of glycine to serine was inhibited by SASP, with 50% inhibition occurring at 0.1 mM. Further evidence of folate antagonism was obtained with the dU suppression test, which depends on the function of a folate-dependent pathway in the de novo synthesis of DNA. Folate antagonists like methotrexate or folate depletion reduces the incorporation of dU into DNA and thus favors incorporation of [3H]thymidine into DNA by an alternate pathway. SASP inhibited the folate-dependent pathway in proliferating virally transformed human lymphocytes (Raji cells). To confirm that SASP acts as a folate antagonist in this system, THF was demonstrated to partly reverse the action of SASP. The significance of this antifolate action by SASP in intact lymphocytes deserves further study in relation to the actions of SASP in patients with inflammatory bowel disease.
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PMID:Antifolate actions of sulfasalazine on intact lymphocytes. 611 49

1 We have investigated the disposition and metabolism of sulphasalazine (SASP) in eight adults with and without inflammatory bowel disease. 2 SASP is poorly absorbed (less than 12%) and the half-time measured in the serum, 10.2 h, is probably the half-time of absorption and therefore an overestimate of the true half-time. The apparent volume of distribution is low (less than 9 l). Renal and biliary clearance rates are low (5.5 and 2.1 ml min-1 respectively) probably due to a high degree of protein binding. Of the absorbed SASP, two thirds is excreted in the urine and one third in the bile. 3 Most of the SASP reaches the colon and is there split by bacteria, forming sulphapyridine (SP) and 5-aminosalicylic acid (5-ASA). 4 SP is almost completely absorbed and, with its metabolites, is excreted in the urine (SP renal clearance rate 32.1 ml min-1). There is no enterohepatic recirculation. 5 Of the 5-ASA released in the colon at least 25% is absorbed and rapidly eliminated in the urine after acetylation. At least 50% is eliminated in the faeces. 6 There are no differences in disposition characteristics when comparing patients with and without inflammatory bowel disease but the metabolism of SASP is markedly reduced in patients taking antibiotics and after removal of the large bowel.
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PMID:The disposition and metabolism of sulphasalazine (salicylazosulphapyridine) in man. 612 76


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