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Journal Der Deutschen Dermatologischen... Jan 2018The sulfone dapsone has an established role in systemic therapy. Its pharmacological and toxicological properties are well known. Topically, dapsone is used in a gel...
BACKGROUND
The sulfone dapsone has an established role in systemic therapy. Its pharmacological and toxicological properties are well known. Topically, dapsone is used in a gel formulation for the treatment of acne vulgaris. In addition, there have been individual case reports on the efficacy of topical dapsone preparations in the treatment of various neutrophilic dermatoses. To date, no finished medicinal product for topical use has been available in Germany.
MATERIAL AND METHODS
Against this background, we set out to develop extemporaneous preparations containing dapsone (5 %) that meet the quality requirements of the European Pharmacopoeia as well as the manufacturing requirements of the German Ordinance on the Operation of Pharmacies (ApBetrO). These formulations included the incorporation of dapsone in a hydrophobic cream base ("hydrophobe Basiscreme DAC") as well as in methylprednisolone aceponate 0.1 % ointment (alternatively, in the latter's cream base without active ingredient).
RESULTS
Tests aimed at investigating the physical, chemical, and microbiological stability of these formulations showed them to meet the aforementioned quality requirements.
CONCLUSION
The extemporaneous formulations presented herein broaden the therapeutic options for topical treatment, in particular for patients with chronic inflammatory dermatoses associated with a neutrophilic pathogenesis.
Topics: Administration, Cutaneous; Dapsone; Drug Combinations; Drug Compounding; Drug Stability; Humans; Methylprednisolone; Ointments; Skin Cream
PubMed: 29280553
DOI: 10.1111/ddg.13409 -
Archives of Dermatology Mar 1993
Topics: Dapsone; Drug Interactions; Drug Monitoring; Humans
PubMed: 8447666
DOI: No ID Found -
Annals of Palliative Medicine Feb 2022First-line medications for acne vulgaris include retinoids and antibiotics. Dapsone is a topical drug approved by the U.S. Food and Drug Administration for the treatment... (Meta-Analysis)
Meta-Analysis
BACKGROUND
First-line medications for acne vulgaris include retinoids and antibiotics. Dapsone is a topical drug approved by the U.S. Food and Drug Administration for the treatment of acne. However, due to its side effects, the clinical application of dapsone has not been promoted, and the value of the medication is still unclear. The aim of this study is to determine the efficacy and safety of dapsone gel in patients with acne.
METHODS
Systematic searches were performed using the following databases on January 4, 2020: PubMed, EMBASE, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure (CNKI), China Biomedical Literature Service System (SinoMed), China Science and Technology Journal Database (CQVIP), and Wanfang Data Knowledge Service Platform. A meta-analysis of randomized controlled trials was then conducted to analyze the efficacy and adverse events of dapsone gel treatment compared with excipient and other drug therapies. RevMan 5.3 software was used to calculate the odds ratio (OR), and the confidence interval (CI) was 95%.
RESULTS
Data of 11,424 participants across 7 trials which met the inclusion criteria were analyzed. Meta-analysis showed that dapsone gel alone or dapsone gel combined with isotretinoin was superior to excipient alone or oral isotretinoin alone in the treatment of acne (OR =1.51, 95% CI: 1.38-1.66, P<0.0001 random effects model, I2=0%). This indicates that dapsone gel is effective for the treatment of acne. We also found that dapsone gel is a more effective treatment for females (OR =1.80, 95% CI: 1.46-2.23). There was no significant difference in the incidence of adverse events between the dapsone group and the control group (OR =0.94, 95% CI: 0.82-1.14, P=0.24 random effects model; I2=29%). The common local adverse reactions in the dapsone group, such as dryness, heat, and eczema, were not statistically significant compared with those in the control group, and the side effects were transient.
DISCUSSION
Dapsone gel is effective in treating acne, and there is no significant difference in adverse events compared with other drugs.
Topics: Acne Vulgaris; Anti-Bacterial Agents; Dapsone; Eczema; Female; Humans; Treatment Outcome; United States
PubMed: 35249339
DOI: 10.21037/apm-21-3935 -
Molecular Pharmaceutics Jul 2019Five anhydrate polymorphs (forms I-V) and the isomorphic dehydrate (Hy) of dapsone (4,4'-diaminodiphenyl sulfone or DDS) were prepared and characterized in an...
Five anhydrate polymorphs (forms I-V) and the isomorphic dehydrate (Hy) of dapsone (4,4'-diaminodiphenyl sulfone or DDS) were prepared and characterized in an interdisciplinary experimental and computational study, elucidating the kinetic and thermodynamic stabilities, solid form interrelationships, and structural features of the known forms I-IV, the novel polymorph form V, and Hy. Calorimetric measurements, solubility experiments, and lattice energy calculations revealed that form V is the thermodynamically stable polymorph from absolute zero to at least 90 °C. At higher temperatures, form II, and then form I, becomes the most stable DDS solid form. The computed 0 K stability order (lattice energy calculations) was confirmed with calorimetric measurements as follows, V (most stable) > III > Hy > II > I > IV (least stable). The discovery of form V was complicated by the fact that the metastable but kinetically stabilized form III shows a higher nucleation and growth rate. By combining laboratory powder X-ray diffraction data and ab initio calculations, the crystal structure of form V ( P2/ c, Z' = 4) was solved, with a high energy DDS conformation allowing a denser packing and more stable intermolecular interactions, rationalizing the formation of a high Z' structure. The structures of the forms I and IV, only observed from the melt and showing distinct packing features compared to the forms II, III, and V, were derived from the computed crystal energy landscapes. Dehydration modeling of the DDS hydrate led to the Hy structure. This study expands our understanding about the complex crystallization behavior of pharmaceuticals and highlights the big challenge in solid form screening, especially that there is no clear end point.
Topics: Absorption, Physicochemical; Calorimetry, Differential Scanning; Chemistry, Pharmaceutical; Computational Chemistry; Crystallization; Dapsone; Drug Stability; Entropy; Hydrogen Bonding; Kinetics; Molecular Conformation; Solubility; Transition Temperature; Water; X-Ray Diffraction
PubMed: 31075201
DOI: 10.1021/acs.molpharmaceut.9b00419 -
Archives of Dermatology Dec 1976Peripheral neuropathy occurred in a 32-year-old man who was receiving dapsone (Aviosulfon) for dermatitis herpetiformis. Neurological examination showed polyneuropathy...
Peripheral neuropathy occurred in a 32-year-old man who was receiving dapsone (Aviosulfon) for dermatitis herpetiformis. Neurological examination showed polyneuropathy that involved the median and ulnar nerves, with a lesser involvement of other peripheral nerves. After treatment with dapsone was discontinued, the neuropathy reversed itself, with practically complete return of function of all nerves involved.
Topics: Adult; Dapsone; Dermatitis Herpetiformis; Humans; Male; Peripheral Nervous System Diseases
PubMed: 188385
DOI: No ID Found -
Archives of Internal Medicine Aug 1967
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International Journal of Dermatology Mar 1981
Topics: Anemia, Hemolytic; Dapsone; Glucosephosphate Dehydrogenase Deficiency; Humans; Leprosy
PubMed: 7216589
DOI: 10.1111/j.1365-4362.1981.tb00415.x -
Leprosy Review Jun 1977
Topics: Dapsone; Drug Resistance, Microbial; Humans; Leprosy; Mycobacterium leprae
PubMed: 330999
DOI: 10.5935/0305-7518.19770016 -
Clinical Pharmacology and Therapeutics Jun 1992Acetylation and N-hydroxylation of dapsone were evaluated in drug-free, non-smoking, normal subjects and subjects with cirrhosis (n = 7 for each group) after oral...
Acetylation and N-hydroxylation of dapsone were evaluated in drug-free, non-smoking, normal subjects and subjects with cirrhosis (n = 7 for each group) after oral administration of 100 mg dapsone. Acetylation was not correlated with oral dapsone clearance or reduced in cirrhosis (0.37 +/- 0.43 versus 0.52 +/- 0.32). Fractional metabolic clearance of dapsone to its hydroxylamine was associated with dapsone oral clearance (r = 0.96, p less than 0.001, n = 14). In patients with cirrhosis, liver disease was associated with a trend to reduction in oral clearance (22%) and metabolic clearance of dapsone (48%). Protein binding was minimally reduced by cirrhosis (73% +/- 1% versus 69% +/- 3% in patients with cirrhosis (p less than 0.02). The dapsone recovery ratio was validated as a phenotypic index of the metabolic clearance of dapsone (r = 0.74, p less than 0.05). In an extended comparison of 14 patients with cirrhosis to 70 control subjects, cirrhosis was associated with reductions of 28% in dapsone recovery ratio (p less than 0.001), and 37% in acetylation ratio (p less than 0.01). Neither dapsone recovery ratio nor acetylation ratio correlated with Pugh Score, conventional liver function tests, indocyanine green clearance, or phenotypic measures of S-mephenytoin hydroxylase or debrisoquin hydroxylase activity. We conclude that cirrhosis is associated with minor changes in dapsone disposition and that dosage modification is not required. In addition, there is evidence that cirrhosis has a selective influence on activity of individual isozymes of cytochrome P450.
Topics: Acetylation; Administration, Oral; Adult; Blood Proteins; Dapsone; Humans; Hydroxylamines; Hydroxylation; Liver Cirrhosis; Liver Cirrhosis, Alcoholic; Middle Aged; Mixed Function Oxygenases
PubMed: 1611807
DOI: 10.1038/clpt.1992.81 -
Scientific Reports Apr 2020Leprosy continues to be the belligerent public health hazard for the causation of high disability and eventual morbidity cases with stable prevalence rates, even with...
Leprosy continues to be the belligerent public health hazard for the causation of high disability and eventual morbidity cases with stable prevalence rates, even with treatment by the on-going multidrug therapy (MDT). Today, dapsone (DDS) resistance has led to fear of leprosy in more unfortunate people of certain developing countries. Herein, DDS was chemically conjugated with five phytochemicals independently as dapsone-phytochemical conjugates (DPCs) based on azo-coupling reaction. Possible biological activities were verified with computational chemistry and quantum mechanics by molecular dynamics simulation program before chemical synthesis and spectral characterizations viz., proton-HNMR, FTIR, UV and LC-MS. The in vivo antileprosy activity was monitored using the 'mouse-foot-pad propagation method', with WHO recommended concentration 0.01% mg/kg each DPC for 12 weeks, and the host-toxicity testing of the active DPC4 was seen in cultured-human-lymphocytes in vitro. One-log bacilli cells in DDS-resistant infected mice footpads decreased by the DPC4, and no bacilli were found in the DDS-sensitive mice hind pads. Additionally, the in vitro host toxicity study also confirmed that the DCP4 up to 5,000 mg/L level was safety for oral administration, since a minor number of dead cells were found in red color under a fluorescent microscope. Several advanced bioinformatics tools could help locate the potential chemical entity, thereby reducing the time and resources required for in vitro and in vitro tests. DPC4 could be used in place of DDS in MDT, evidenced from in vivo antileprosy activity and in vitro host toxicity study.
Topics: Computer Simulation; Dapsone; Humans; Leprostatic Agents; Leprosy; Mycobacterium leprae; Phytochemicals
PubMed: 32322091
DOI: 10.1038/s41598-020-63913-9