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Platelets 2015Dapsone is one of the second line treatments of immune thrombocytopenic purpura (ITP). Dapsone is cheap and has response rates comparable to other second line treatment...
Dapsone is one of the second line treatments of immune thrombocytopenic purpura (ITP). Dapsone is cheap and has response rates comparable to other second line treatment options like azathioprine, danazol, cyclophosphamide, cyclosporine, and vincristine. This retrospective analysis includes 38 patients (out of total 313 patients) of ITP treated with dapsone from 2004 to 2012. All male patients were screened for G6PD deficiency before starting dapsone. Out of 38 patients (12 children and 26 adults), one was newly diagnosed ITP, seven were persistent ITP, and 30 were chronic ITP. Five patients had side effects of dapsone; two required discontinuation due to skin rashes. The average dose of dapsone was 1.57 mg/kg/day and time to response was 57 days (19-108 days). The response was irrespective of previous treatments and response to them. The response rate was 48.6% (complete response = 40.5%). Only two adult patients had sustained response (> 6 months) after dapsone discontinuation. There were no predictors identified for dapsone response. Dapsone is a safe and cheap second-line therapy for ITP with a response rate of about 50% (majority being CR). A response to dapsone is slow, sustained, and relapses are uncommon on therapy. Dapsone withdrawal leads to relapse in most of the patients.
Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Dapsone; Erythrocyte Indices; Female; Follow-Up Studies; Humans; Male; Middle Aged; Platelet Count; Purpura, Thrombocytopenic, Idiopathic; Retrospective Studies; Time Factors; Treatment Outcome; Young Adult
PubMed: 24512442
DOI: 10.3109/09537104.2014.886677 -
Journal of Pharmaceutical Sciences Jul 2020Poor solubility and low dissolution rate of pharmaceuticals in many cases largely limit their bioavailability and efficacy. One of the promising approaches to improve...
Poor solubility and low dissolution rate of pharmaceuticals in many cases largely limit their bioavailability and efficacy. One of the promising approaches to improve dissolution behavior is to develop new multicomponent solid forms. Herein we use this strategy to synthesize new multicomponent solids of dapsone (DAP), which belongs to BCS class IV, with a series of hydroxybenzoic acid coformers. A new salt of DAP with 2,6-dihydroxybenzoic acid (26DHBA) and 4 eutectics with other hydroxybenzoic acids were reported through comprehensive characterizations using powder X-ray diffraction DSC, and vibrational spectroscopy techniques. The salt formation was evidenced by the presence of ionic interactions detected using FT-IR and Raman spectroscopy, and the stoichiometric ratio was determined to be 1:1. Binary phase diagrams were established to determine the composition of eutectics. The cause for salt and eutectic selection was further understood by computing molecular electrostatic potential (MEP) surface where 26DHBA shows the greatest acidity. Moreover, the powder dissolution study and microenvironment pH measurement reveal that both salt and eutectics of DAP display improvements on the dissolution rate and equilibrium concentration in which the acidity of coformers plays a dominant role. Our findings provide a direction for future coformer screening of multicomponent solids with improved pharmaceutical properties.
Topics: Calorimetry, Differential Scanning; Crystallization; Dapsone; Hydroxybenzoates; Solubility; Spectroscopy, Fourier Transform Infrared; X-Ray Diffraction
PubMed: 32294458
DOI: 10.1016/j.xphs.2020.04.003 -
International Journal of Molecular... Dec 2022Dapsone (DDS) therapy can frequently lead to hematological side effects, such as methemoglobinemia and DNA damage. In this study, we aim to evaluate the protective...
Dapsone (DDS) therapy can frequently lead to hematological side effects, such as methemoglobinemia and DNA damage. In this study, we aim to evaluate the protective effect of racemic alpha lipoic acid (ALA) and its enantiomers on methemoglobin induction. The pre- and post-treatment of erythrocytes with ALA, ALA isomers, or MB (methylene blue), and treatment with DDS-NOH (apsone hydroxylamine) was performed to assess the protective and inhibiting effect on methemoglobin (MetHb) formation. Methemoglobin percentage and DNA damage caused by dapsone and its metabolites were also determined by the comet assay. We also evaluated oxidative parameters such as SOD, GSH, TEAC (Trolox equivalent antioxidant capacity) and MDA (malondialdehyde). In pretreatment, ALA showed the best protector effect in 2.5 µg/mL of DDS-NOH. ALA (1000 µM) was able to inhibit the induced MetHb formation even at the highest concentrations of DDS-NOH. All ALA tested concentrations (100 and 1000 µM) were able to inhibit ROS and CAT activity, and induced increases in GSH production. ALA also showed an effect on DNA damage induced by DDS-NOH (2.5 µg/mL). Both isomers were able to inhibit MetHb formation and the S-ALA was able to elevate GSH levels by stimulating the production of this antioxidant. In post-treatment with the R-ALA, this enantiomer inhibited MetHb formation and increased GSH levels. The pretreatment with R-ALA or S-ALA prevented the increase in SOD and decrease in TEAC, while R-ALA decreased the levels of MDA; and this pretreatment with R-ALA or S-ALA showed the effect of ALA enantiomers on DNA damage. These data show that ALA can be used in future therapies in patients who use dapsone chronically, including leprosy patients.
Topics: Methemoglobin; Antioxidants; Thioctic Acid; Dapsone; Superoxide Dismutase; DNA Damage
PubMed: 36613503
DOI: 10.3390/ijms24010057 -
Chemistry and Physics of Lipids Sep 2021The increase in antimicrobial resistance has created a crisis that has become top priority for global policy and public health. Antibiotics are constantly being rendered...
The increase in antimicrobial resistance has created a crisis that has become top priority for global policy and public health. Antibiotics are constantly being rendered in-effective due to the emergence of bacterial resistance; therefore, novel strategies for improving therapeutic efficacies of existing drugs must be focused. Advancements in nanotechnology have opened up new avenues for enhancing therapeutic efficacy of existing drugs via construction of intelligent and efficient delivery systems. This study reports the synthesis of Dapsone based nonionic surfactant and its utilization as delivery system for Ceftriaxone sodium. The synthesized nonionic surfactant was characterized via mass spectrometry and H NMR and IR spectroscopic techniques. The drug loaded vesicles of newly synthesized sulfur based nonionic were formed through thin film hydration method and characterized for drug entrapment efficiency, vesicles size, zeta potential, morphology using UV-vis spectrometry, dynamic light scattering (DLS) and atomic force microscopic (AFM) techniques. The biocompatibility of newly synthesized surfactant was assessed using blood hemolysis and in-vitro cells cytotoxicity. Antibacterial potential of drug loaded vesicles was assessed in gram positive and gram negative bacterial cultures. The spectroscopic results confirm successful synthesis of novel sulfur based nonionic surfactant that formed spherical shaped drug loaded vesicles with an average size of 97.95 ± 3.45 nm and 56.3 ± 3.15 % entrapment of the model drug (Ceftriaxone sodium). The vesicles displayed negative surface charge of -16.8 ± 3.72 mV and released the entrapped drug in a controlled way in-vitro drug release. The drug loaded vesicular formulation showed enhanced cellular uptake and greater antibacterial potentials when compared with control. Results of this study show that the Dapsone based surfactant is safe, biocompatible, non-toxic and can be used as promising vesicular carrier for enhancing therapeutic efficacy of antibacterial drug, Ceftriaxone sodium.
Topics: Anti-Bacterial Agents; Biocompatible Materials; Biofilms; Dapsone; Drug Carriers; Drug Liberation; Gram-Negative Bacteria; Gram-Positive Bacteria; Hemolysis; Humans; Micelles; Microbial Sensitivity Tests; Particle Size; Sulfur; Surface-Active Agents
PubMed: 34252425
DOI: 10.1016/j.chemphyslip.2021.105115 -
Pediatrics Sep 2022Immunoglobulin A vasculitis (IgAV) is a systemic small-vessel vasculitis. Although corticosteroids (CS) are the primary treatment for gastrointestinal manifestations... (Observational Study)
Observational Study
Immunoglobulin A vasculitis (IgAV) is a systemic small-vessel vasculitis. Although corticosteroids (CS) are the primary treatment for gastrointestinal manifestations associated with IgAV, some patients develop refractory or recurrent symptoms such as vomiting and abdominal pain despite CS treatment. Dapsone, a synthetic sulfone antimicrobial, has been used to treat cutaneous purpura in IgAV, but few authors have reported its use for refractory gastrointestinal symptoms. In this retrospective observational study, we describe results in 7 children with IgAV who were treated with dapsone for abdominal pain resistant to CS. Dapsone rapidly relieved abdominal pain in all 7 patients, who then were tapered off CS without relapse. Side effects of mild methemoglobinemia and hemolysis appeared to be manageable with planned monitoring and dose adjustment; a single patient who discontinued dapsone had fatigue and hypoxia associated with methemoglobinemia. No side effects were life-threatening. Dapsone may be considered as a therapeutic option for gastrointestinal symptoms refractory to CS in children with IgAV.
Topics: Abdominal Pain; Adrenal Cortex Hormones; Child; Dapsone; Gastrointestinal Diseases; Humans; IgA Vasculitis; Immunoglobulin A; Methemoglobinemia; Vasculitis
PubMed: 35975615
DOI: 10.1542/peds.2021-055884 -
Current Computer-aided Drug Design 2021Lactoperoxidase (LPO) is a member of the mammalian heme peroxidase family and is an enzyme of the innate immune system. It possesses a covalently linked heme prosthetic...
INTRODUCTION
Lactoperoxidase (LPO) is a member of the mammalian heme peroxidase family and is an enzyme of the innate immune system. It possesses a covalently linked heme prosthetic group (a derivative of protoporphyrin IX) in its active site. LPO catalyzes the oxidation of halides and pseudohalides in the presence of hydrogen peroxide (HO) and shows a broad range of the antimicrobial activity.
METHODS
In this study, we have used two pharmaceutically important drug molecules, namely dapsone and propofol, which were earlier reported as potent inhibitors of LPO. At the same time, the stereochemistry and mode of binding of dapsone and propofol to LPO are still not known because of the lack of the crystal structures of LPO with these two drugs. In order to fill this gap, we utilized molecular docking and molecular dynamics (MD) simulation studies of LPO in its native and complex forms with dapsone and propofol.
RESULTS
From the docking results, the estimated binding free energies (ΔG) of -9.25 kcal/mol (Ki = 0.16 μM) and -7.05 kcal/mol (Ki = 6.79 μM) were observed for dapsone, and propofol, respectively. The standard error of the Auto Dock program is 2.5 kcal/mol; therefore, molecular docking results alone were inconclusive.
CONCLUSION
To further validate the docking results, we performed MD simulation on unbound, and two drugs bounded LPO structures. Interestingly, MD simulations results explained that the structural stability of LPO-Propofol complex was higher than LPO-Dapsone complex. The results obtained from this study establish the mode of binding and interaction pattern of the dapsone and propofol to LPO as inhibitors.
Topics: Animals; Dapsone; Hydrogen Peroxide; Lactoperoxidase; Molecular Docking Simulation; Propofol
PubMed: 32598266
DOI: 10.2174/1573409916666200628104134 -
Dermatology (Basel, Switzerland) 2016Pustular psoriasis is an uncommon psoriasis variant, clinically characterized as small sterile pustules on an erythematous base. Evidence for therapy is lacking, and... (Review)
Review
BACKGROUND
Pustular psoriasis is an uncommon psoriasis variant, clinically characterized as small sterile pustules on an erythematous base. Evidence for therapy is lacking, and many currently employed systemic therapeutics carry risks of significant side effects, without specifically targeting disease etiology which includes the aggregation of neutrophils.
OBSERVATIONS
We report therapy with the anti-neutrophil agent dapsone in 5 patients with pustular psoriasis and provide a brief review of the literature. Four patients responded to oral dapsone and 1 to topical dapsone therapy. All 5 patients had previously failed multiple topical and systemic treatments. In 2 cases, oral dapsone allowed for the discontinuation of other systemic agents. One patient stopped oral dapsone due to a side effect of sleep disturbance.
CONCLUSION
Dapsone has a much safer side effect profile and may target the pathophysiology of pustular psoriasis more directly than many other systemic agents. As such, dapsone should be considered for the treatment of patients with pustular psoriasis.
Topics: Adult; Aged; Antimalarials; Dapsone; Female; Humans; Male; Middle Aged; Psoriasis; Skin Diseases, Vesiculobullous
PubMed: 26465742
DOI: 10.1159/000431171 -
Combinatorial Chemistry & High... 2024Severe SARS-CoV-2 infection is linked with an overstated immune response with the succeeding release of pro-inflammatory cytokines and progression of the cytokine storm.... (Review)
Review
Severe SARS-CoV-2 infection is linked with an overstated immune response with the succeeding release of pro-inflammatory cytokines and progression of the cytokine storm. In addition, severe SARS-CoV-2 infection is associated with the development of oxidative stress and coagulopathy. Dapsone (DPS) is a bacteriostatic antibiotic that has a potent anti-inflammatory effect. Thus, this mini-review aimed to elucidate the potential role of DPS in mitigating inflammatory disorders in COVID-19 patients. DPS inhibits neutrophil myeloperoxidase, inflammation, and neutrophil chemotaxis. Therefore, DPS could be effective against neutrophilia-induced complications in COVID-19. In addition, DPS could be effective in mitigating inflammatory and oxidative stress disorders by suppressing the expression of inflammatory signaling pathways and the generation of reactive oxygen species (ROS) correspondingly. In conclusion, DPS might be effective in the management of COVID-19 through the attenuation of inflammatory disorders. Therefore, preclinical and clinical studies are reasonable in this regard.
Topics: Humans; Dapsone; COVID-19 Drug Treatment; Inflammation; COVID-19; SARS-CoV-2; Oxidative Stress; Neutrophils; Anti-Inflammatory Agents; Reactive Oxygen Species
PubMed: 36999691
DOI: 10.2174/1386207326666230331121735 -
Skinmed 2021
Topics: Dapsone; Dermatologic Agents; Humans
PubMed: 34861925
DOI: No ID Found -
The British Journal of Dermatology Oct 2020
Topics: Dapsone; Hidradenitis Suppurativa; Humans
PubMed: 32294243
DOI: 10.1111/bjd.19136