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Redox Report : Communications in Free... 2010Sulfasalazine is a prodrug composed by a molecule of 5-aminosalicylic acid (5-ASA) and sulfapyridine (SP), linked by an azo bond, which has been shown to be effective in...
Sulfasalazine is a prodrug composed by a molecule of 5-aminosalicylic acid (5-ASA) and sulfapyridine (SP), linked by an azo bond, which has been shown to be effective in the therapy of inflammatory bowel diseases (IBD) such as ulcerative colitis and Crohn's disease, as well as of rheumatic diseases, such as rheumatoid arthritis and ankylosing spondylitis. The precise mechanism of action of sulfasalazine and/or its metabolites has not been completely elucidated, though its antioxidant effects are well established and are probably due to its scavenging effects against reactive oxygen and nitrogen species (ROS and RNS), as well as metal chelating properties, in association to its inhibitory effects over neutrophil oxidative burst. The present work was focused on screening and comparing the potential scavenging activity for an array of ROS (O(2)(•-), H(2)O(2), (1)O(2), ROO(•) and HOCl) and RNS ((•)NO and ONOO(-)), mediated by sulfasalazine and its metabolites 5-ASA and SP, using validated in vitro screening systems. The results showed that both 5-ASA and sulfasalazine were able to scavenge all the tested ROS while SP was practically ineffective in all the assays. For HOCl, (1)O(2), and ROO(•), 5-ASA showed the best scavenging effects. A new and important finding of the present study was the strong scavenging effect of 5-ASA against (1)O(2). 5-ASA was shown to be a strong scavenger of (•)NO and ONOO(-). Sulfasalazine was also able to scavenge these RNS, although with a much lower potency than 5-ASA. SP was unable to scavenge (•)NO in the tested concentrations but was shown to scavenge ONOO(-), with a higher strength when the assay was performed in the presence of 25 mM bicarbonate, suggesting further scavenging of oxidizing carbonate radical. In conclusion, the ROS- and RNS-scavenging effects of sulfasalazine and its metabolites shown in this study may contribute to the anti-inflammatory effects mediated by sulfasalazine through the prevention of the oxidative/nitrative/nitrosative damages caused by these species.
Topics: Aminosalicylic Acid; Hydrogen Peroxide; Molecular Structure; Reactive Nitrogen Species; Reactive Oxygen Species; Sulfapyridine; Sulfasalazine; Superoxides
PubMed: 21208525
DOI: 10.1179/135100010X12826446921707 -
Annals of the Rheumatic Diseases Jul 2009To determine the efficacy and safety of etanercept and etanercept plus sulfasalazine versus sulfasalazine in patients with rheumatoid arthritis (RA) despite... (Randomized Controlled Trial)
Randomized Controlled Trial
Efficacy, safety and patient-reported outcomes of combination etanercept and sulfasalazine versus etanercept alone in patients with rheumatoid arthritis: a double-blind randomised 2-year study.
OBJECTIVE
To determine the efficacy and safety of etanercept and etanercept plus sulfasalazine versus sulfasalazine in patients with rheumatoid arthritis (RA) despite sulfasalazine therapy.
METHODS
Patients were randomly assigned to etanercept (25 mg twice weekly; sulfasalazine was discontinued at baseline), etanercept plus sulfasalazine (unchanged regimen of 2-3 g/day) or sulfasalazine in a double-blind, randomised, 2-year study in adult patients with active RA despite sulfasalazine therapy. Efficacy was assessed using the American College of Rheumatology criteria, disease activity scores (DAS) and patient-reported outcomes (PRO).
RESULTS
Demographic variables and baseline disease characteristics were comparable among treatment groups; mean DAS 5.1, 5.2 and 5.1 for etanercept (n = 103), etanercept plus sulfasalazine (n = 101) and sulfasalazine (n = 50), respectively. Withdrawal due to lack of efficacy was highest with sulfasalazine (26 (52%) vs 6 (6%) for either etanercept group, p<0.001). Patients receiving etanercept or etanercept plus sulfasalazine had a more rapid initial response, which was sustained at 2 years, than those receiving sulfasalazine: mean DAS 2.8, 2.5 versus 4.5, respectively (p<0.05); ACR 20 response was achieved by 67%, 77% versus 34% of patients, respectively (p<0.01) Overall, PRO followed a similar pattern; a clinically significant improvement in health assessment questionnaire was achieved by 76%, 78% versus 40% of patients, respectively (p<0.01). Commonly reported adverse events occurring in the etanercept groups were injection site reactions and pharyngitis/laryngitis (p<0.01).
CONCLUSION
Etanercept and etanercept plus sulfasalazine are efficacious for the long-term management of patients with RA. The addition of etanercept or substitution with etanercept should be considered as treatment options for patients not adequately responding to sulfasalazine.
Topics: Adolescent; Adult; Aged; Antirheumatic Agents; Arthritis, Rheumatoid; Double-Blind Method; Drug Therapy, Combination; Etanercept; Female; Humans; Immunoglobulin G; Male; Middle Aged; Receptors, Tumor Necrosis Factor; Sulfasalazine; Treatment Outcome; Young Adult
PubMed: 18794178
DOI: 10.1136/ard.2007.087106 -
Environmental Health Perspectives Feb 1997
Topics: Animals; Birth Weight; Body Weight; Dose-Response Relationship, Drug; Female; Fetal Death; Gastrointestinal Agents; Kidney; Litter Size; Male; Organ Size; Pregnancy; Rats; Rats, Sprague-Dawley; Reproduction; Sperm Count; Spermatozoa; Sulfasalazine; Testis; Thyroid Gland
PubMed: 9114353
DOI: No ID Found -
Medicine Aug 2022Drug hypersensitivity syndrome (DHS) induced by sulfasalazine is a serious systemic delayed adverse drug reaction, which is associated with significant morbidity and...
INTRODUCTION
Drug hypersensitivity syndrome (DHS) induced by sulfasalazine is a serious systemic delayed adverse drug reaction, which is associated with significant morbidity and mortality.
PATIENT CONCERNS
A 52-year-old man was hospitalized for developing a rash after 3 weeks of sulfasalazine treatment for ulcerative colitis (UC).
DIAGNOSIS
The patient was diagnosed with DHS based on his drug history, clinical manifestations, and laboratory test results.
INTERVENTIONS
The patient was administered intravenous glucocorticoids. The patient's condition improved after treatment with human immunoglobulin and antihistamines.
OUTCOMES
Combination therapy of glucocorticoid and gamma globulin, the whole-body pruritus disappeared, and no new rash appeared. The whole-body rash subsided or turned dark red.
CONCLUSION
This article describes the diagnosis and treatment process of a case of sulfasalazine-induced DHS and reviews the relevant literature to improve clinician understanding and avoid misdiagnosis and missed diagnosis.
Topics: Colitis, Ulcerative; Drug Hypersensitivity; Drug Hypersensitivity Syndrome; Exanthema; Humans; Male; Middle Aged; Sulfasalazine
PubMed: 35984191
DOI: 10.1097/MD.0000000000030060 -
International Journal of Pharmaceutics Mar 2016The aim of this in vivo study was to assess the ability of the prodrug conjugate diclofenac-β-cyclodextrin to release diclofenac in the colon following oral...
The aim of this in vivo study was to assess the ability of the prodrug conjugate diclofenac-β-cyclodextrin to release diclofenac in the colon following oral administration, using sulfapyridine (a metabolite of sulfasalazine) as a marker of colonic absorption. Two groups of rats were used; the test rats received a suspension containing the two prodrugs, diclofenac-β-cyclodextrin and sulfasalazine, while the control rats received a suspension containing the corresponding free drugs, sodium diclofenac and sulfapyridine. The rats were fasted overnight with free access to water before and throughout the first 12h of the study. Blood was collected from the tail vein at pre-determined time points and the plasma analyzed for the concentrations of diclofenac and sulfapyridine. Following the oral administration of the two prodrugs, a more extended absorption profile was observed and Cmax was achieved 10h post-dose, in contrast to rapid absorption of the free drugs (tmax of diclofenac being 1.3h, and that of sulfapyridine being 2.1h). In addition to a later tmax, conjugation of diclofenac to β-cyclodextrin also resulted in a reduced Cmax and a reduced AUC. The same tmax for diclofenac-β-cyclodextrin as for sulfasalazine confirms the colonic metabolism of diclofenac-β-cyclodextrin. This study shows the potential of this new cyclodextrin-based prodrug to target and release diclofenac specifically in the colon following oral administration.
Topics: Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Colon; Diclofenac; Drug Delivery Systems; Drug Liberation; Intestinal Absorption; Male; Prodrugs; Rats, Wistar; Sulfasalazine; beta-Cyclodextrins
PubMed: 26784980
DOI: 10.1016/j.ijpharm.2016.01.024 -
British Medical Journal (Clinical... Jan 1981
Topics: Adult; Aged; Child; Desensitization, Immunologic; Drug Hypersensitivity; Female; Humans; Male; Sulfasalazine
PubMed: 6109553
DOI: 10.1136/bmj.282.6258.110 -
World Journal of Gastroenterology Oct 2006Mesalazine is a safe drug, although adverse events may be seen in a minority of patients. This applies also to pregnant women and children. The role of mesalazine in... (Review)
Review
Mesalazine is a safe drug, although adverse events may be seen in a minority of patients. This applies also to pregnant women and children. The role of mesalazine in combination therapy to improve efficacy and concomitant drug pharmacokinetics, or in chemoprevention against inflammatory bowel disease (IBD)-related colonic carcinoma has not yet been completely elucidated. Therapeutic success of mesalazine may be optimized by a combination of high dose and low frequency of dosage to improve compliance. Therefore, due to its superior safety profile and pharmacokinetic characteristics, mesalazine is preferable to sulphasalazine. This paper reviews the literature concerning mechanisms of action, indications and off-label use, pharmacokinetic properties and formulations, therapeutic efficacy, compliance, paediatric indications, chemoprevention, and safety issues and adverse event profile of mesalazine treatment versus sulphasalazine. It also highlights these controversies in order to clarify the potential benefits of mesalazines in IBD therapy and evidence for its use.
Topics: Adenocarcinoma; Anti-Inflammatory Agents, Non-Steroidal; Colonic Neoplasms; Humans; Inflammatory Bowel Diseases; Mesalamine; Sulfasalazine; Treatment Failure; Treatment Refusal
PubMed: 17036381
DOI: 10.3748/wjg.v12.i38.6115 -
ChemMedChem Sep 2021The xCT antiporter is a cell membrane protein involved in active counter-transportation of glutamate (outflux) with cystine (influx) over the human cell membrane. This...
The xCT antiporter is a cell membrane protein involved in active counter-transportation of glutamate (outflux) with cystine (influx) over the human cell membrane. This feature makes the xCT antiporter a crucial element of the biosynthesis of the vital free radical scavenger glutathione. The prodrug sulfasalazine, a medication for the treatment of ulcerative colitis, was previously proven to inhibit the xCT antiporter. Starting from sulfasalazine, a molecular scaffold jumping followed by SAR-assisted design and synthesis provided a series of styryl hydroxy-benzoic acid analogues that were biologically tested in vitro for their ability to decrease intracellular glutathione levels using four different cancer cell lines: A172 (glioma), A375 (melanoma), U87 (glioma) and MCF7 (breast carcinoma). Depletion of glutathione levels varied among the compounds as well as among the cell lines. Flow cytometry using propidium iodide and the annexin V marker demonstrated minimal toxicity in normal human astrocytes for a promising candidate molecule (E)-5-(2-([1,1'-biphenyl]-4-yl)vinyl)-2-hydroxybenzoic acid.
Topics: Amino Acid Transport System y+; Drug Design; Humans; Molecular Structure; Prodrugs; Structure-Activity Relationship; Sulfasalazine
PubMed: 33847044
DOI: 10.1002/cmdc.202100204 -
Revista Espanola de Enfermedades... Jun 2021Aminosalicylates (5-ASA) are used as the first-line maintenance treatment in patients with mild-moderate ulcerative colitis (UC). Early identification of patients at... (Review)
Review
Aminosalicylates (5-ASA) are used as the first-line maintenance treatment in patients with mild-moderate ulcerative colitis (UC). Early identification of patients at high risk for 5-ASA non-response and appropriate therapeutic escalation are essential to avoid disease progression. However, the absence of a standardized definition for treatment success makes this a challenging task. The focus of the current review was to describe the risk factors and management strategies associated with 5-ASA non-response. Rates of 5-ASA failure can vary from 17 % to 75 % according to different success definitions, of which clinical relapse is the most prevalent and studied condition. Younger age and endoscopic activity at diagnosis, extensive colitis, early need for corticosteroids, elevated inflammatory markers and non-adherence are consistent risk factors of 5-ASA failure. Given the effectiveness, safety profile and tolerability of this medication, therapy optimization is critical before treatment escalation. Combined use of systemic and topical therapy at an appropriate dose in a once-daily administration and control of adherence could improve success rates.
Topics: Administration, Oral; Anti-Inflammatory Agents, Non-Steroidal; Colitis, Ulcerative; Humans; Mesalamine; Risk Factors; Sulfasalazine
PubMed: 33569968
DOI: 10.17235/reed.2021.7797/2021 -
Indian Journal of Pharmacology 2021The objectives were to evaluate drug rash with eosinophilia and systemic symptoms syndrome due to sulfasalazine and to carry out the pharmacoeconomic assessment...
The objectives were to evaluate drug rash with eosinophilia and systemic symptoms syndrome due to sulfasalazine and to carry out the pharmacoeconomic assessment associated with this adverse drug reaction (ADR). A 37-year woman was presented with rashes, fever, cough, and dyspnea. In the past 3 months, she was on sulfasalazine for inflammatory polyarthritis and seronegative spondyloarthritis. The diagnosis was based on raised eosinophils count, breathing difficulty, and typical pattern of rashes. Significant improvement was seen after discontinuation of sulfasalazine and with the initiation of parenteral corticosteroids. The casualty of this ADR was "probable" based on RegiSCAR, WHO, and Naranjo casualty assessment scales. Preventability, severity was assessed and total cost for management of the ADR was found to be ' 12,126. Thus, ADRs not only adds to patient sufferings but also increase the economic burden. Health-care providers need to be made aware of potentially fatal ADRs associated with sulfa drugs and should be keen to report such ADRs to drug safety authorities.
Topics: Adrenal Cortex Hormones; Adult; Diagnosis, Differential; Drug Hypersensitivity Syndrome; Eosinophilia; Female; Fever; Humans; Spondylarthritis; Sulfasalazine
PubMed: 34854409
DOI: 10.4103/ijp.IJP_129_18