Sulfasalazine Research Articles

Coated Mesalazine is as Effective as Sulfasalazine

Coated Mesalazine is as Effective as Sulfasalazine

Interaction of metronidazole with phenobarbital, cimetidine, prednisone, and sulfasalazine in Crohn's disease.

The influence of prednisone(PR), sulfasalazine(SZ), cimetidine(CM), and phenobarbital(PB) on the pharmacokinetics of metronidazole was investigated in six Crohn's patients. Metronidazole was first administered alone (250 mg bid, po) and then with prednisone (10 mg bid, po), sulfasalazine (1 g bid, po), cimetidine (600 mg bid) or phenobarbital (60 mg bid, po). Each regimen was followed for 6 days and sampling of blood and urine was carried out on the 7th day after the first dose of each regimen. Plasma and urine samples were analysed for the drug and its two principal metabolites, hydroxymetronidazole and metronidazole-1-acetic acid, by HPLC. When given alone, metronidazole had a mean volume of distribution of 0.667 +/- 0.15 lkg-1, a half-life of 9.7 +/- 3.1 h and an oral clearance of 0.852 +/- 0.23 (ml-1 min) kg-1. The disposition kinetics of metronidazole and its metabolites was not altered by CM and SZ. Induction of metabolism of metronidazole by PR was made manifest in significant increases in oral clearance of the former and urinary excretion of the hydroxy metabolite, and significant decrease in AUC of the parent compound. PB also induced the metabolism of metronidazole. This induction was reflected in significant increases in the oral clearance of metronidazole and AUC of the hydroxy metabolite as well as significant decreases in AUC, half-life, and urinary excretion of the parent drug.

Sulphasalazine Increases Fibrinolysis in the Anaesthetised Rat

Sulphasalazine Increases Fibrinolysis in the Anaesthetised Rat

Possible mode of action of 5-aminosalicylic acid.

Despite the extensive use of sulfasalazine (SAS) and/or 5-aminosalicylic acid (5-ASA) in patients with inflammatory bowel disease and, more recently, rheumatoid arthritis, their mode of action has not been elucidated so far. None of the numerous pharmacological and biochemical effects described, including immunosuppressive, antifolate, and modulatory actions on lymphocyte and leukocyte functions, could be defined unequivocally as mediating their beneficial activity. Recently, interest has focused on actions of SAS and 5-ASA on the various enzymes of the arachidonic acid cascade. Mucosa of patients with inflammatory bowel disease generates excessive amounts of cyclooxygenase products such as prostaglandins (PG) as well as 5-lipoxygenase products such as leukotriene (LT) B4 and sulfidopeptide-LT. Both PG and LT exert proinflammatory actions and are potentially important mediators of mucosal inflammation. SAS and 5-ASA, however, have been found to inhibit PG synthesis under certain experimental conditions only, while increasing PG formation under other conditions. While SAS was found to inhibit colonic LTB4 synthesis, 5-ASA was reported to selectively affect the cyclooxygenase pathway of arachidonate metabolism in this tissue. Our results demonstrate that, like the parent compound, the metabolite 5-ASA in a dose-dependent manner inhibits release of LTB4 and sulfidopeptide-LT from normal human colonic mucosa (IC50 3.5 and 3.7 mmol/liter, respectively). Indomethacin, which has no efficacy in the treatment of patients with inflammatory bowel disease, on the other hand, selectively inhibited PGE2 formation in normal and inflamed colonic mucosa (IC50 1.7 and 1.0 mmol/liter, respectively) without reducing synthesis of LTB4 or sulfidopeptide-LT.(ABSTRACT TRUNCATED AT 250 WORDS)

Salazosulfapyridine and metabolites in fetal and maternal body fluids with special reference to 5-aminosalicylic acid.

In 7 pregnant women, treated prophylactically with salazosulfapyridine (SASP) 3 g/day, amniotic fluid (16th week, n = 4, maternal and cord plasma (n = 5) and breast milk (n = 3) were analysed for SASP and the metabolites sulfapyridine (SP), acetyl sulfapyridine (Ac-SP), 5-aminosalicylic acid (5-ASA) and acetyl 5-aminosalicylic acid (Ac-5-ASA). Amniotic fluid contained concentrations of SASP, SP and Ac-SP and partly also Ac-5-ASA comparable to those previously found by others, whereas 5-ASA concentrations were very low. The ratios of maternal to cord plasma for all SASP metabolites were about 1:1-1:2, except for 5-ASA, cord plasma being extremely low. In breast milk, only traces of 5-ASA were detected, while Ac-5-ASA was above the plasma level. Only negligible amounts of 5-ASA are thus transferred to the fetus/newborn, which is of significance for the future use of the new non-sulfa-containing 5-ASA preparations during and after pregnancy.

Sulfasalazine May Have A Use In Ankylosing Spondylitis

Sulfasalazine May Have A Use In Ankylosing Spondylitis

IMPORTANCE OF COLONIC MUCOSAL BIOPSIES IN THE DIAGNOSIS OF INFLAMMATORY BOWEL DISEASE (IBD) IN CHILDREN AND ADOLESCENTS

The diagnosis of IBD is usually based on historic, radiologic, endoscopic, and histologic evidence of mucosal disease. 8 children (ages 7-17 yrs; 2M, 6F) evaluated for abdominal complaints [abdominal pain (7), diarrhea (6), bloody stools (3), fever (1), perianal rash (1), abdominal distention (1), anorexia (1)] were found to have abnormal rectal biopsies but normal hemograms (8/8), serum albumin and total protein (7/7), and contrast radiographs of the upper and lower intestinal tracts (8/8). Sigmoidoscopy, abnormal in 5/8, showed mild friability (3/8) and a single superficial ulceration (1/8). Mucosal biopsies showed edema, chronic inflammatory changes, or focal hemorrhage in the lamina propria. The 6 treated with sulfasalazine (SAS) (mean 7.4 mos) improved. When SAS was discontinued, 4 relapsed with recurrence of initial symptoms (mean 9 mos). At the time of relapse chronic ulcerative colitis was diagnosed in 2, 1 had normal barium contrast studies and colonoscopic biopsies, and 1 is undiagnosed. Of the untreated patients 1 is well and 1 has chronic ulcerative colitis radiographically and histologically. 3 have not relapsed during followup (mean 13.3 mos). Conclusions: 1) Abnormal colonic mucosal biopsies in patients with recurrent abdominal pain and diarrhea, even with normal laboratory, radiographic, and sigmoidoscopic studies, suggest the presence of IBD. 2) Mucosal biopsies should be part of the evaluation of patients with recurrent abdominal pain even if sigmoidoscopy is normal.

Costs of Sulfasalazine and Metronidazole

Costs of Sulfasalazine and Metronidazole

Will There Be a Next Generation of Sulfasalazine?

Will There Be a Next Generation of Sulfasalazine?

Sperm size in patients with inflammatory bowel disease on sulfasalazine therapy

The size of the heads of spermatozoa from eight men with chronic inflammatory bowel disease (IBD) treated with sulfasalazine (SS) were measured by image analysis. These were compared with the size of sperm heads from noncolitic men with normal semen indices and with the sperm head size of noncolitic oligospermic men. The patients on SS therapy had a significantly larger sperm head size for the 99th percentile than the noncolitic oligospermic men. After withdrawal of the drug, sperm head size increased further before becoming smaller. The size did not return to that of the sperm of men with normal semen indices during the period studied. Possible mechanisms for the increase in sperm size are discussed and its association with the reversible infertility caused by SS medication.

Absorption, enterohepatic circulation, and excretion of 5-aminosalicylic acid in rats.

After oral administration of sulfasalazine, the majority of the administered dose reaches the colon, where it is split into 5-aminosalicylic acid (5-ASA) and sulfapyridine. 5-ASA is believed to be the effective component in the treatment of inflammatory bowel disease. After intraduodenal administration of 5-ASA (20 mg) in rats, 91% of the drug was absorbed in the proximal small intestine. Peak serum 5-ASA concentration (55 micrograms/ml) was reached in 1 h. Approximately 61 and 6% of the administered dose were excreted in the urine and bile, respectively, in 24 h, almost exclusively in the acetylated form. When sulfapyridine (20 mg) was administered in addition to 5-ASA, 70% of the sulfapyridine was absorbed in the small intestine, peak serum concentration (50 micrograms/ml) was reached in 1 h, and 30% of the administered dose was excreted in the urine in 24 h. The results indicate that after oral administration of 5-ASA, a therapeutically significant concentration of the drug is not expected in the terminal ileum which is a common site of involvement in Crohn's disease. The therapeutic implications of these findings are discussed herein.

Oral tests in contact allergy to para-amino compounds.

A group of 34 inpatients with contact allergy to para‐amino compounds (sulfanilamide, paraphenylenediamine, benzocaine) underwent a series of peroral tests using structurally related substances, sulphonvl ureas (carbutamide, tolbutamide and chlorpropamide), diaminodi‐phenyl‐sulfone. saccharin and salicyl azosulfapyridine. Sulphonyl ureas given orally can produce a widespread dermatitis in subjects with contact sensitivity to sulfanilamide. but not in those sensitized to paraphenylenediamine and benzocaine.

Infertility from sulfasalazine seems only temporary

Infertility from sulfasalazine seems only temporary

What makes sulfasalazine work?

What makes sulfasalazine work?

Inhibition of prostaglandin biosynthesis by sulphasalazine and its metabolites

Sulphasalazine (SZ) inhibits prostaglandin (PG) biosynthesis in vitro with a potency comparable to that of aceylsalicylate. The metabolites of SZ, sulphapyridine and 5-aminosalicylic acid, were of considerably lower potency as inhibitors of PG biosynthesis in the synthetase preparations used. The inhibition of prostaglandin production by SZ could at least partly account for the clinical utility of sulphasalazine in ulcerative colitis. Sulphapyridine may help to maintain inhibitory concentrations of SZ by restraining bacterial breakdown of the active drug.

Chronic Inflammatory Bowel Disease.

Chronic inflammatory bowel disease (IBD) encompasses the disease entities, ulcerative colitis (UC) and Crohn's disease (CD). An aetiologic agent has not yet been defined and the diagnosis is based, therefore, on the sum of clinical, paraclinical, radiologic, endoscopic and histopathologic features. In recent years pathogenetic studies have focused on immune mechanisms, transmissible infectious agents, the potential role of the normal intestinal flora, dietary factors, enzymatic alterations and genetic features, in addition to vascular, neuromotor, allergic and psychologic factors. The corner stones in medical therapy of IBD are still corticosteroids and sulphasalazine (SAZ). The new oral salicylates, which are analogues of SAZ or "slow release" preparations of 5-aminosalicylic acid (mesalazine), have provided a therapeutic progress, because they are tolerated better than SAZ. Immunosuppressive agents, such as azathioprine and 6-mercaptopurine, reduce the requirement for corticosteroids and are effective in refractory CD, but the effect is delayed up to several months. The therapeutic action of cyclosporine A is not sustained, but often associated with side effects. Metronidazole has a beneficial effect on perineal disease. The efficacy of antimycobacterial drugs, sodium-cromoglycate, lidocaine, clonidine and sucralfate has been reported only in optimistic case stories and small open trials. A diet, rich in omega-3-fatty acids, modifies leukotriene (LT) production, but its clinical efficacy is insufficient. The first anti-leukotriene-drug, zileuton, has recently been evaluated and a significant, although insufficient, clinical response was obtained by a 70 per cent inhibition of rectal LTB4 synthesis. Dietary therapy may be useful as an adjunct to treatment of local complications in CD.(ABSTRACT TRUNCATED AT 250 WORDS)

Distribution Studies of Salicylazosulfapyridine and its Metabolites

Previous studies in the rat have indicated that the initial reaction of salicylazosulfapyridine (SAS) metabolism, reduction of the azo bond, can be attributed exclusively to the action of the intestinal bacteria. This finding raises questions concerning the amount of intact SAS that reaches its possible site of action within the lumen in inflammatory disease of the lower intestine. Accordingly, a study of the distribution of SAS and its metabolites in the rat and in man has been undertaken. In both species only small amounts of SAS were recovered in the urine. The drug was not recovered in the feces of rats but small amounts were found in the feces of 4 of 11 human subjects. In both species a consistent finding was high levels of sulfapyridine in the urine and high levels of 5-aminosalicylate in the feces. Indeed the level of 5aminosalicylate in rat feces greatly exceeded that found when an equimolar amount of 5-aminosalicylate itself was fed orally to the rats. These studies indicate that SAS is almost completely metabolized in both human subjects and rats and that there is a tendency for its metabolite 5-aminosalicylate to reach relatively high levels in the feces.

Studies of Intestinal Microflora

Summary Quantitative and qualitative microbiological studies of the stools were carried out in 25 patients with untreated ulcerative colitis and regional enteritis. The mild to moderately ill patients with idiopathic ulcerative colitis were noted to harbor a fecal microflora very similar to that of healthy individuals. However, those with regional enteritis and severe ulcerative colitis had increased numbers of colif orms in their stools. Treatment of ulcerative colitis with salicylazosulf apyridine (Azulfidine) tended to increase the numbers of some microbial species, especially Gram-positive forms. These changes did not appear to be related to the severity of disease or the effectiveness of treatment. In a group of normal individuals receiving drug or placebo in a double blind study, salicylazosulf apyridine caused no definite alterations in the fecal microflora. Systemic corticosteroid therapy of ulcerative colitis resulted in little change in the intestinal flora. Modest decreases in the number of fecal colif orms appeared to be associated with clinical improvement.

Outline of colloid chemistry. I

In the present study, heterogeneous electro-Fenton (EF) process was applied to remove the sulfasalazine (SU) pharmaceutical from aqueous solutions. In the first part, 3D graphene loaded with [email protected]2O3 core-shell nanowires ([email protected]2O3/3D-GO) was used as a cathode electrode in the EF process. Graphene oxide (GO) was synthesized for the synthesis of 3D graphene nanocomposites using the improved Hummers’ method and subsequently 3D graphene synthesized by the hydrothermal method using glycine. Finally, [email protected]2O3/3D-GO composite was synthesized and its properties were assessed by Scanning electron microscopy, Atomic force microscopy, Brunauer–Emmett–Teller, Fourier-transform infrared spectroscopy and X-ray diffraction methods. Then, the cathode electrode was prepared using the resulting composite and its performance was evaluated using Cyclic Voltammetry analysis. In the final part of this work, the [email protected]2O3/3D-GO electrode was used as the cathode electrode in the heterogeneous EF process to remove SU from aqueous solutions. The effect of operating parameters such as applied current (mA), initial pH of solution, initial pharmaceutical concentration (mg L−1) and process time (min) on pharmaceutical removal efficiency under heterogeneous EF process was investigated by response surface methodology. The results showed that the optimum values for applied current, pH, initial pharmaceutical concentration and electrolysis time were respectively 300 mA, 7, 30 mg L−1 and 100 min, resulting 99.60% of SU removal. Finally, the intermediates of SU degradation were determined by Gas chromatography–mass spectrometry analysis and the amount of mineralization was determined by total organic carbon analysis. About 5.2% drop in the SU removal efficiency was observed within 8 operational runs.