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Journal of Pediatric Gastroenterology... Apr 2023Sulfasalazine (SZ) is commonly used to treat pediatric ulcerative colitis (UC). SZ can be compounded into a suspension form which is beneficial for children with... (Observational Study)
Observational Study
BACKGROUND
Sulfasalazine (SZ) is commonly used to treat pediatric ulcerative colitis (UC). SZ can be compounded into a suspension form which is beneficial for children with difficulty swallowing a pill. Despite being utilized for over 40 years, there is a lack of published data on the efficacy and safety of SZ suspension in children with UC. Recently, third-party payors have begun refusing to pay for SZ suspension due to lack of data.
METHODS
In this retrospective study, we reviewed the electronic medical records of patients ages <18 years diagnosed with UC from June 1999 to December 2019 at Boston Children's Hospital and treated with SZ suspension as a first-line agent. We obtained demographics, clinical, and endoscopic data to measure outcomes at 1 year and long term.
RESULTS
Of 57 patients treated with SZ suspension, 52 (91%) had a follow-up and 26 of 52 (50%) remained in steroid-free remission at 1 year. Two patients were switched to SZ tablets due to nonmedical reasons and 11 (21%) required rescue treatment (2 infliximab, 1 tacrolimus, 8 6-mercaptopurine/azathioprine) within a year. Three required colectomy within a year and 5 in long term. Four (8%) developed nonserious adverse reactions and switched to 5-aminosalicylates (5-ASA) by 1 year. The median duration of long-term follow-up was 36 months (range, 2-205 months) with 28 requiring treatment escalation in long term.
CONCLUSIONS
SZ suspension is a safe and effective treatment for UC in children with difficulty swallowing a pill. The 1-year remission rate on this treatment is comparable to 5-ASA utilized in children.
Topics: Adolescent; Child; Humans; Azathioprine; Colitis, Ulcerative; Immunosuppressive Agents; Infliximab; Mesalamine; Retrospective Studies; Sulfasalazine; Treatment Outcome
PubMed: 36576855
DOI: 10.1097/MPG.0000000000003698 -
Renal Failure 2016Sulfasalazine is widely used for inflammatory-mediated disorders in human. Renal damage is a serious adverse effect accompanied sulfasalazine administration. No specific...
Sulfasalazine is widely used for inflammatory-mediated disorders in human. Renal damage is a serious adverse effect accompanied sulfasalazine administration. No specific therapeutic option is available against this complication so far. Oxidative stress seems to play a role in sulfasalazine-induced renal injury. Current investigation was designed to evaluate the effect of N-acetyl cysteine (NAC) and dithiothreitol (DTT) as thiol reductants against sulfasalazine-induced renal injury in rats. Oral administration of sulfasalazine (600 mg/kg for 14 consecutive days) caused renal injury as judged by increase in serum level of creatinine and blood urea nitrogen. Furthermore, the level of reactive oxygen species and lipid peroxidation were raised in kidney tissue after sulfasalazine administration. Additionally, it was also found that renal glutathione reservoirs were significantly depleted in sulfasalazine-treated animals. Histopathological examination of kidney endorsed organ injury in drug-treated rats. Daily intraperitoneal administration of NAC (250 and 500 mg/kg/day) and/or DTT (15 and 30 mg/kg/day) effectively alleviated renal damage induced by sulfasalazine. Data suggested that thiol reductants could serve as potential protective agents with therapeutic capabilities against sulfasalazine adverse effect toward kidney.
Topics: Acetylcysteine; Acute Kidney Injury; Animals; Antirheumatic Agents; Dithiothreitol; Drug Evaluation, Preclinical; Free Radical Scavengers; Male; Random Allocation; Rats, Sprague-Dawley; Sulfasalazine
PubMed: 26479898
DOI: 10.3109/0886022X.2015.1096731 -
Journal of AOAC International Jan 2024Sulfasalazine and pentoxifylline are co-prescribed together to treat psoriasis and pemphigus vulgaris. Sulfasalazine is an anti-inflammatory, immunosuppressant, and...
BACKGROUND
Sulfasalazine and pentoxifylline are co-prescribed together to treat psoriasis and pemphigus vulgaris. Sulfasalazine is an anti-inflammatory, immunosuppressant, and antibiotic drug, while pentoxifylline is a vasodilator and immunosuppressant. The spectra of the two drugs and plasma suffer from severe overlap.
OBJECTIVE
This work aims to simultaneously determine sulfasalazine and pentoxifylline in their binary mixture and spiked human plasma by the assessment of their UV spectral data.
METHODS
Two model updated chemometric methods were established using principal component regression and partial least-squares regression models. The two models were validated in accordance with the U.S. Food and Drug Administration guidelines for bioanalysis and were applied for the determination of both drugs in synthetic mixtures or spiked human plasma.
RESULTS
Accuracy and precision were within the accepted limits. In addition, three different assessment methods were used to evaluate the environmental greenness of the proposed models.
CONCLUSION
The two updated models are simple, rapid, sensitive, and precise, and could be easily applied in QC laboratories for determination of sulfasalazine and pentoxifylline, without any preliminary separation steps or interference from plasma matrix.
HIGHLIGHTS
Two updated chemometric models called principlal component regression and partial least-squares regression were established for determination of sulfasalazine and pentoxifylline in spiked human plasma using UV spectrophotometric data.
Topics: Humans; Pharmaceutical Preparations; Pentoxifylline; Sulfasalazine; Spectrophotometry; Least-Squares Analysis; Immunosuppressive Agents
PubMed: 37610330
DOI: 10.1093/jaoacint/qsad097 -
Zeitschrift Fur Rheumatologie Nov 2017The perioperative management of patients on immunosuppressive drugs is uncertain due to a lack of controlled studies. Continuation of medication without a pause may... (Review)
Review
The perioperative management of patients on immunosuppressive drugs is uncertain due to a lack of controlled studies. Continuation of medication without a pause may increase the risk of postoperative infections and wound healing disorders and when the pause is too long this can induce a flare of the underlying rheumatic disease. Additional factors, such as rheumatic disease activity, comorbidities, previous infections and the type of surgical procedure also modulate the risk. The highest risk of infection is associated with corticosteroids depending on the dose, so that a dosage as low as possible but stable in the perioperative period is recommended. Among the conventional disease-modifying antirheumatic drugs (DMARDs) only methotrexate has been sufficiently investigated and in this case a pause in treatment induces higher risks than continuation. Antimalarial agents and sulphasalazine should be continued due to the low risks, whereas leflunomide should be washed out before major surgical interventions. The perioperative risk of treatment with biologics is still far from clear; therefore, as a rule of thumb, withholding treatment for two serum half-lives before an intervention and restarting after completed wound healing are recommended.
Topics: Adrenal Cortex Hormones; Antimalarials; Antirheumatic Agents; Arthritis, Rheumatoid; Arthroplasty, Replacement; Biological Products; Humans; Immunosuppressive Agents; Isoxazoles; Leflunomide; Methotrexate; Perioperative Care; Risk Factors; Sulfasalazine; Surgical Wound Infection; Wound Healing
PubMed: 28913596
DOI: 10.1007/s00393-017-0379-0 -
Chemical Biology & Drug Design Oct 2023This study aimed to explore the potential mechanism by which sulfasalazine (SAS) inhibits esophageal cancer cell proliferation. A cell counting kit-8 (CCK-8) assay was...
This study aimed to explore the potential mechanism by which sulfasalazine (SAS) inhibits esophageal cancer cell proliferation. A cell counting kit-8 (CCK-8) assay was used to detect the effect of SAS (0, 1, 2, and 4 mM) on the proliferation of TE-1 cells. Subsequently, TE-1 cells were divided into control group, SAS group, SAS + ferrostatin-1 (ferroptosis inhibitor) group, and SAS + Z-VAD (OH)-FMK (apoptosis inhibitor) group, and cell proliferation was measured using a CCK-8 assay. Real-time quantitative polymerase chain reaction and western blotting were used to determine the expression of solute carrier family member 7 11 (SLC7A11, also called xCT), glutathione peroxidase 4 (GPX4), and acyl-CoA synthase long-chain family member 4 (ACSL4) in TE-1 cells. Measurement of ferroptosis in TE-1 cells was achieved by flow cytometry. Compared with the control group (0 mM SAS), the proliferation of TE-1 cells was significantly inhibited by different concentrations of SAS for different time lengths, and 4 mM SAS treatment for 48 h could obtain the maximum inhibition rate (53.9%). In addition, SAS treatment caused a significant decrease in the mRNA and protein expression of xCT and GPX4, and a significant increase in ACSL4 expression in TE-1 cells treated with SAS. Flow cytometry results showed that the ferroptosis level was significantly increased after SAS treatment. However, the activation of ferroptosis by SAS was partially eliminated by treatment with ferrostatin-1 or Z-VAD (OH)-FMK. In conclusion, SAS inhibits the proliferation of esophageal carcinoma cells by activating the ferroptosis pathway.
Topics: Humans; Sulfasalazine; Ferroptosis; Cell Proliferation; Esophageal Neoplasms; Receptor Protein-Tyrosine Kinases
PubMed: 37291716
DOI: 10.1111/cbdd.14281 -
Clinical and Experimental Rheumatology 2017The aim of this study was to characterise the use and costs of subsidising conventional disease-modifying anti-rheumatic drugs (DMARDs) and biologic DMARDs in Australia...
OBJECTIVES
The aim of this study was to characterise the use and costs of subsidising conventional disease-modifying anti-rheumatic drugs (DMARDs) and biologic DMARDs in Australia from 2004-2014 through pharmaceutical benefits schemes.
METHODS
Dispensing and expenditure data on conventional and biologic DMARDs were extracted from Medicare Australia and temporal trends were analysed. Medicine use was standardised in terms of the defined daily dose (DDD) per 1,000 population per day (DDD/1,000 population/day).
RESULTS
Conventional and biologic DMARD use increased 74% over the study period (4.86 to 8.46 DDD/1,000 population/day; average annual increase 6.7%). Conventional DMARDs accounted for the vast majority of total use and increased 55% (4.81 to 7.43 DDD/1,000 population/day), while biologic DMARD use increased 1,784% (0.055 to 1.030 DDD/1,000 population/day). The most frequently used conventional DMARD was methotrexate (56% total conventional DMARD use) and use increased 95%. Hydroxychloroquine and leflunomide use increased marginally while sulfasalazine use declined 4.2%. Etanercept was the most commonly used biologic DMARD in 2004 and adalimumab in 2014. Conventional DMARD expenditure decreased 4.2% to AUD$33.3 million but biologic DMARD expenditure increased 2,089% to AUD$585.4 million.
CONCLUSIONS
The use of conventional and biologic DMARDs increased substantially over a decade in Australia. Patterns of use of conventional DMARDs have changed, and costs have decreased. In contrast a significant escalation in both the use and cost of biologic DMARDs has occurred. Further research is required to address cost-effectiveness, regulation and quality use of these medicines in clinical practice.
Topics: Antirheumatic Agents; Arthritis, Psoriatic; Arthritis, Rheumatoid; Biological Products; Drug Costs; Drug Utilization; Etanercept; Humans; Methotrexate; Practice Patterns, Physicians'; Spondylitis, Ankylosing; Sulfasalazine
PubMed: 28421991
DOI: No ID Found -
Nihon Rinsho. Japanese Journal of... Jun 2016Conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) other than methotrexate (MTX: anchor csDMARDs) are effective for single use, reinforcement of... (Review)
Review
Conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) other than methotrexate (MTX: anchor csDMARDs) are effective for single use, reinforcement of MTX, biologics and induction and maintenance of biologics-free condition. Newly developed iguratimod (IGU) does not suppress immunological reaction, therefore, it is useful for single use or combination with other csDMARDs in patients with complications. IGU can be used as a first csDMARDs before MTX use during the screening for MTX. IGU might be effective for reinforcement of MTX, biologics and induction and maintenance of biologics-free condition just like other csDMARDs. IGU can be used in wide variety of situation of the treatment of rheumatoid arthritis and it is desired that after the all-case surveillance condition for approval, IGU become a standard csDMARDs all over the world which was made in Japan.
Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Chromones; Cysteine; Drug Discovery; Drug Interactions; Drug Substitution; Drug Therapy, Combination; Drugs, Generic; Female; Humans; Male; Ribonucleosides; Sulfasalazine; Sulfonamides; Tacrolimus
PubMed: 27311184
DOI: No ID Found -
International Journal of Molecular... Jul 2023Ovarian clear cell carcinoma (OCCC) is a rare subtype of epithelial ovarian carcinoma that responds poorly to chemotherapy. Glutathione (GSH) is a primary antioxidant,...
Ovarian clear cell carcinoma (OCCC) is a rare subtype of epithelial ovarian carcinoma that responds poorly to chemotherapy. Glutathione (GSH) is a primary antioxidant, which protects cells against reactive oxygen species (ROS). High levels of GSH are related to chemotherapeutic resistance. The glutamine/cystine transporter xCT is essential for intracellular GSH synthesis. However, whether xCT inhibition can overcome the resistance to chemotherapeutic agents in OCCC remains unclear. This study demonstrated that combined treatment with paclitaxel (PTX) and the xCT inhibitor sulfasalazine (SAS) significantly enhanced cytotoxicity more than the individual drugs did in OCCC cells. Treatment with PTX and SAS induced apoptosis more effectively than did individual drug treatments in the cells with significant generation of ROS. Moreover, combined treatment with PTX and SAS induced ferroptosis in the cells with low expression of glutathione peroxidase (GPx4), high levels of intracellular iron and significant lipid ROS accumulation. Therefore, our findings provide valuable information that the xCT inhibitor might be a promising therapeutic target for drug-resistant OCCC. The strategy of combined administration of PTX and SAS can potentially be used to treat OCCC and help to develop novel therapeutic methods.
Topics: Humans; Paclitaxel; Reactive Oxygen Species; Cell Line, Tumor; Cell Death; Sulfasalazine; Glutathione; Carcinoma
PubMed: 37511540
DOI: 10.3390/ijms241411781 -
Scientific Reports Feb 2020N-acetyltransferase 2 (NAT2) acetylator status can be classified into three groups depending on the number of rapid alleles (e.g., NAT2*4): rapid, intermediate, and slow... (Meta-Analysis)
Meta-Analysis
N-acetyltransferase 2 (NAT2) acetylator status can be classified into three groups depending on the number of rapid alleles (e.g., NAT2*4): rapid, intermediate, and slow acetylators. Such acetylator status may influence the occurrence of adverse drug reactions (ADRs) during sulfasalazine treatment. This systematic review and meta-analysis aimed to evaluate the association between NAT2 acetylator status and ADRs of sulfasalazine. We searched for qualified studies in PubMed, Web of Science, Embase, and the Cochrane Library. Odds ratio (OR) and 95% confidence intervals (CIs) were calculated to evaluate the strength of the association between NAT2 acetylator status and ADRs of sulfasalazine. Nine cohort studies involving 1,077 patients were included in the meta-analysis. NAT2 slow acetylators were associated with an increase in overall ADRs (OR 3.37, 95% CI: 1.43 to 7.93; p = 0.005), discontinuation due to overall ADRs (OR 2.89, 95% CI: 1.72 to 4.86; p < 0.0001), and dose-related ADRs (OR 5.20, 95% CI: 2.44 to 11.08; p < 0.0001), compared with rapid and intermediate acetylators. In conclusion, NAT2 slow acetylators are at risk of ADRs during sulfasalazine treatment. Based on our findings, NAT2 genotyping may be useful to predict the occurrence of ADRs during sulfasalazine treatment.
Topics: Arylamine N-Acetyltransferase; Humans; Polymorphism, Genetic; Sulfasalazine
PubMed: 32107440
DOI: 10.1038/s41598-020-60467-8 -
Reproduction, Fertility, and Development May 2023Sulfasalazine (SAS) is a drug prescribed for pregnant and breastfeeding women with chronic inflammatory bowel diseases. SAS treatment induces transitory infertility in...
CONTEXT
Sulfasalazine (SAS) is a drug prescribed for pregnant and breastfeeding women with chronic inflammatory bowel diseases. SAS treatment induces transitory infertility in both adult men and male rats. Although SAS crosses the placenta and passes into maternal milk, the consequences of maternal SAS exposure on the reproductive development of male offspring needs further study.
AIMS
The current study evaluated whether maternal SAS exposure interferes with the reproductive development of male rat offspring in the neonatal, infant, pubertal and adulthood periods.
METHODS
Pregnant Wistar rats (n =10/group) received 300mg/kg/day of SAS dissolved in carboxymethyl cellulose (CMC), by gavage, from gestational day 0 to lactation day 21, and 3mg/kg/day of folic acid during gestation. The control group received CMC.
KEY RESULTS
During puberty, maternal SAS exposure increased the total length of seminiferous tubules, and round cells were observed in the lumen of caput and cauda epididymis. Moreover, SAS induced oxidative stress-related alterations in the testes of infant and adolescent rats.
CONCLUSIONS
Although maternal SAS treatment caused reproductive alterations in infant and adolescent male rats, in adulthood, there were no impairments in sperm parameters that could compromise fertility.
IMPLICATIONS
This study investigated the consequences of maternal exposure to SAS on the reproductive development of male rat offspring from birth to adulthood, employing a human-relevant dose. Thus, this study provides information for better understanding of SAS treatment during critical periods of development.
Topics: Humans; Pregnancy; Male; Rats; Female; Animals; Adolescent; Sulfasalazine; Breast Feeding; Rats, Wistar; Prenatal Exposure Delayed Effects; Semen; Lactation; Maternal Exposure
PubMed: 37080254
DOI: 10.1071/RD22240