Disease relevance of Sulphapyridine

• We studied the therapeutic efficacy of sulfasalazine and its metabolites sulfapyridine and 5-aminosalicylic acid in nine patients with Crohn's disease and in 23 patients with ulcerative colitis [1].
• Although the sulfones or sulfapyridine have been the mainstay of treatment, it is now clear that the skin disease responds to strict adherence to a gluten-free diet [2].
• All side effects except skin rash were associated with a mean serum total sulfapyridine concentration of 62.9 +/- 17.4 micrograms/ml and free sulfapyridine concentration of 42 +/- 9.5 micrograms/ml [3].
• Suppositories of sulphapyridine, 5-aminosalicylic acid, and placebo were used in 45 patients with idiopathic proctitis to determine the active part of sulphasalazine [4].
• Acetylation polymorphism of sulfapyridine in patients with ulcerative colitis and Crohn's disease [5].

High impact information on Sulphapyridine

• Timing of the sulfapyridine signal corresponded to the arrival of 5%-13% of technetium 99m DTPA in the cecum [6].
• Twenty to fifty percent of the absorbed drug was excreted in bile as SASP and no detectable sulfapyridine appeared in the bile [7].
• We investigated the effects of sulfasalazine (SSZ) and its metabolites, sulfapyridine (SP) and 5-aminosalicylic acid (5-ASA), on components of angiogenesis, namely, endothelial cell (EC) chemotaxis and proliferation, as well as on EC chemokine and soluble adhesion molecule expression [8].
• Treatment with sulfasalazine or sulfapyridine, but not 5-aminosalicyclic acid, inhibits basic fibroblast growth factor-induced endothelial cell chemotaxis [8].
• In conclusion, in vivo treatment with sulphasalazine inhibits the in vitro natural killer cell activity and this seems to be mediated by the sulphapyridine moiety [9].

Chemical compound and disease context of Sulphapyridine

• Inhibition of leucocyte motility may explain why sulphasalazine and 5 amino-salicylic acid are effective in ulcerative colitis while sulphapyridine is not [10].
• Abnormalities attributable to nutritional deficiency were detected in only 6 of the 86, whereas drug-associated hematological or biochemical changes were present in 36 of 55 subjects treated with dapsone or sulfapyridine [11].
• The sulfapyridine component of the sulfasalazine was the likely causative agent because 41 years earlier, the patient had experienced fever, myalgias, and eosinophilia after taking a sulfonamide [12].
• At the end of treatment, body weights were reduced in higher dose groups of sulfasalazine, CH 74A and sulfapyridine compared to control animals [13].
• Sulfasalazine is metabolized variably to sulfapyridine, a sulphonamide known to be an effective therapy for dermatitis herpetiformis but no longer available [14].

Biological context of Sulphapyridine

• Rats fed the metabolite sulphapyridine also had a reduced litter size when mated, while those fed the metabolite 5'aminosalicylic acid and a polymer of 5'aminosalicylic acid did not [15].
• It was shown that sulfapyridine shares the same acetylation polymorphism as sulfadimidine [5].
• Salivary excretion and pharmacokinetics of sulfapyridine after sulfasalazine [16].
• Sulphapyridine metabolism is largely determined by inherited acetylator phenotype, either slow or fast [17].
• The formed sulphapyridine is almost completely absorbed and eliminated by hydroxylation, glucuronidation and polymorphic acetylation [18].

Anatomical context of Sulphapyridine

• The time course of the drug's effect on semen quality is consistent with the hypothesis that sulphasalazine or a metabolite, possibly sulphapyridine, is directly toxic to developing spermatozoa [19].
• Another approach to deliver the active 5-ASA to the gastrointestinal tract is accomplished with novel 'prodrugs' of 5-ASA, in which the carrier molecule sulphapyridine is replaced by 5-ASA itself (azodisalicylate) or other compounds [18].
• Those related to high concentrations of sulphapyridine and to poor acetylation of the drug include gastrointestinal intolerance, malaise, headache, arthralgia, drug fever, effects on red blood cells and reversible male infertility [20].
• Effect of sulphasalazine and sulphapyridine on neutrophil superoxide production: role of cytosolic free calcium [21].
• It is designed to deliver 5-aminosalicylic acid to the colonic mucosa without the sulfapyridine-associated side-effects encountered with sulfasalazine [22].

Associations of Sulphapyridine with other chemical compounds

• The appearance of sulfapyridine in plasma after oral administration of salicylazosulfapyridine (SASP) was evaluated as a method for defining arrival time in the cecum, an index of small bowel transit [6].
• The response to indomethacin, hydrocortisone, sulphasalazine, sulphapyridine, and 5-ASA was not dependent on the HLA type of the patients, disease activity, or drug therapy [23].
• Sulphasalazine serves as a vehicle to deliver its possible active components, 5-aminosalicylic acid and sulphapyridine, to the colon in higher concentrations than could be achieved by oral administration of either one alone [17].
• Thus, age is a determinant of the steady-state concentrations of salicylate moieties but acetylator phenotype plays a greater role in determining the serum concentration of sulfapyridine, which has greater therapeutic implications in rheumatology [24].
• These studies demonstrate that dapsone, diasone, and sulfapyridine inhibit both neutrophil iodination and cytotoxicity for tumor cells, while other sulfonamides have no effect [25].

Gene context of Sulphapyridine

• OBJECTIVES: 5-Aminosalicylate is metabolized in colonic mucosa by N-acetyltransferase 1 (NAT1), and sulfapyridine is metabolized in the liver by N-acetyltransferase 2 (NAT2) [26].
• Sulphapyridine significantly reduced TNF and induced IL-1 release in a dose-dependent fashion, but had no significant effect on IL-6 release [27].
• 4. In contrast, 5ASA and sulfapyridine neither inhibit NF-kappaB/Rel activation nor induce apoptosis in T-lymphocytes at doses up to 5.0 mM [28].
• The aim of the present study was to investigate if sulfasalazine and its colonic metabolites 5-aminosalicylic acid (5ASA) and sulfapyridine affect NF-kappaB/Rel activation and viability of T-lymphocytes [28].
• Neither of the cleavage products of sulfasalazine (5-aminosalicylate and sulfapyridine) inhibited thromboxane synthetase although 5-aminosalicylate blocked cyclooxygenase (IC50 = 5 mM) [29].

Analytical, diagnostic and therapeutic context of Sulphapyridine

• Seventy-five to ninety percent of the drug was excreted in ileostomy effluents of 6 patients as SASP, and only 5% of the dose was sulfapyridine [7].
• The subsequent HPLC analysis of collected blood samples allowed the appearance of sulfapyridine in the plasma and hence the arrival of sulfasalazine in the colon to be determined [30].
• Determination of salicylazosulphapyridine and sulphapyridine in plasma using high-performance liquid chromatography [31].
• The total transit time was shortened to 8 days after treatment with sulphapyridine at a dosage of 450 mg kg-1 for 38-52 days [32].
• Electron-capture gas chromatography of sulphapyridine and its N4-acetyl metabolite in serum after extraction methylation [33].

References