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Dermatologic Clinics Jul 2010After synthesis of dapsone (4,4' diaminodiphenylsulfone) in 1908, the compound was known exclusively in chemistry. Following the epoch-making discovery of the...
After synthesis of dapsone (4,4' diaminodiphenylsulfone) in 1908, the compound was known exclusively in chemistry. Following the epoch-making discovery of the antimicrobial potential for sulfonamides emerged, the sulfone class was included in the medical armamentarium. The therapeutic role of sulfones related to both pathogen-caused diseases and chronic inflammatory dermatoses has led to extensive use in dermatology. At present dapsone is the only sulfone congener available for clinical practice. The sulfone is used in rifampin-based multiple-drug regiments to treat multibacillary and paucibacillary leprosy and to treat Pneumocystis jiroveci pneumonia and prevent toxoplasmosis in individuals with AIDS. In dermatology, dapsone is the preferred drug for treating dermatitis herpetiformis (Duhring's disease) and is useful in the management of a broad range of chronic inflammatory entities, especially autoimmune bullous disorders. With proper administration and monitoring, the sulfone should be considered a useful and safe agent.
Topics: Adult; Anti-Infective Agents; Autoimmune Diseases; Child; Dapsone; Humans; Hypersensitivity; Jaundice; Leprosy; Orphan Drug Production; Peripheral Nervous System Diseases; Pneumocystis carinii; Pneumonia, Pneumocystis; Skin Diseases; Therapies, Investigational; Toxoplasmosis
PubMed: 20510768
DOI: 10.1016/j.det.2010.03.014 -
The Journal of Pharmacy and Pharmacology Feb 1992Administration of dapsone in combination with trimethoprim and cimetidine to male rats resulted in a marked decrease (P less than 0.05) in measured methaemoglobin levels...
Administration of dapsone in combination with trimethoprim and cimetidine to male rats resulted in a marked decrease (P less than 0.05) in measured methaemoglobin levels (46.2 +/- 24% Met Hb h) compared with administration of dapsone alone (124.5 +/- 24.4% Met Hb h). The elimination half-life of dapsone (814 +/- 351 min) was more than doubled in the presence of trimethoprim and cimetidine compared with control (355 +/- 160 min, P less than 0.05). However, there were no significant differences in AUC and clearance when dapsone was administered in combination with trimethoprim and cimetidine compared with dapsone alone. Co-administration of trimethoprim with dapsone in the absence of cimetidine did not affect either methaemoglobin formation, AUCs, half-lives, or clearance values of dapsone compared with control. There was a threefold increase in the AUC of trimethoprim (6296 +/- 2249 micrograms min mL-1) in the presence of dapsone compared with trimethoprim alone (2122 +/- 552 micrograms min mL-1). There was also a corresponding decrease in the clearance of trimethoprim in the presence of dapsone compared with control (19.1 +/- 6.9 vs 60.8 +/- 21.0 mL min-1). However, there was no change in the elimination half-life of trimethoprim between the two experimental groups (273 +/- 120 vs 292 +/- 54 min). The AUC of trimethoprim increased more than threefold in the presence of cimetidine (7100 +/- 1501 micrograms min mL-1) compared with trimethoprim alone (2122 +/- 552 micrograms min mL-1).(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Acetylation; Animals; Cimetidine; Dapsone; Drug Interactions; Half-Life; Male; Methemoglobin; Methemoglobinemia; Rats; Rats, Inbred Strains; Trimethoprim
PubMed: 1352810
DOI: 10.1111/j.2042-7158.1992.tb03573.x -
Archives of Dermatology Mar 1984A severe motor and a minor sensory neuropathy developed in a man being treated with dapsone (4,4'-diaminodiphenylsulfone) for dermatitis herpetiformis. He had received...
A severe motor and a minor sensory neuropathy developed in a man being treated with dapsone (4,4'-diaminodiphenylsulfone) for dermatitis herpetiformis. He had received dapsone for 16 years before any signs of neurotoxicity became evident. Electrodiagnostic and clinical features were consistent with an axonal neuropathy. Clinical characteristics of dapsone-induced neuropathy include a motor neuropathy affecting the extremities, usual onset within five years after the initiation of dapsone therapy, dapsone dosage usually equal to or greater than 300 mg/day, and, almost always, complete recovery from the neuropathy after dapsone-dose reduction or withdrawal. The patient was found to be a slow acetylator of sulfamethazine, and therefore is a slow acetylator of dapsone. An HLA typing was done on the patient. New cases of dapsone-induced neuropathy should be HLA typed and have acetylation profiles in an attempt to identify future high-risk patients. This case is noteworthy for the length of time of dapsone usage (16 years) and the low daily dosage of dapsone (100 mg) taken prior to the development of neuropathy.
Topics: Adult; Dapsone; Dermatitis Herpetiformis; Electromyography; Humans; Male; Muscular Atrophy; Peripheral Nervous System Diseases
PubMed: 6322702
DOI: No ID Found -
International Journal of Pharmaceutics Dec 2019The main objective of this study was to develop, characterize and evaluate the potential use of dapsone-loaded nanostructured lipid carriers (NLCs) as a topical...
The main objective of this study was to develop, characterize and evaluate the potential use of dapsone-loaded nanostructured lipid carriers (NLCs) as a topical treatment for acne. Differently charged NLC formulations were successfully prepared using an emulsification/sonication method. The particle sizes ranged from 106.2 ± 5.6 nm to 151.3 ± 7.4 nm, and the NLCs possessed the predicted surface charges, depending on the emulsifier used (Tween 80, Transcutol P, or cetyltrimethylammonium bromide). The entrapment efficiencies ranged from 76.5 ± 3.8% to 91.1 ± 3.9%. Selected formulations were assessed for possible interactions, in vitro release, ex vivo skin permeation, pharmacological efficacy and safety compared with a hydroalcoholic solution. Dapsone was embedded in the lipid matrix of NLCs and behaved as controlled release system with a good occlusive effect. Dapsone-loaded cationic NLC formulation enhanced the skin permeation of dapsone, increase the amount of dapsone retained in the skin in controlled manner, and improved the anti-rosacea activity. Based on these encouraging results, cationic NLC represents a promising carrier for the safe topical delivery of dapsone.
Topics: Administration, Topical; Animals; Dapsone; Drug Carriers; Drug Delivery Systems; Drug Liberation; Lipids; Mice; Nanoparticles; Nanostructures; Particle Size; Skin; Skin Absorption
PubMed: 31715347
DOI: 10.1016/j.ijpharm.2019.118781 -
Leprosy Review Dec 1995A case of dapsone syndrome occurring in a Filipino man under treatment for multibacillary (MB) leprosy is described. The patient manifested progressive fever,...
A case of dapsone syndrome occurring in a Filipino man under treatment for multibacillary (MB) leprosy is described. The patient manifested progressive fever, erythroderma and jaundice 4 weeks after initiation of multidrug therapy (MDT) with rifampicin, clofazimine and dapsone. The clinical symptoms conformed well to the dapsone syndrome first described in the 1950s and this report proves that the syndrome does still exist. There was recovery after dapsone was omitted and therapy with systemic corticosteroids was started. In view of this potentially fatal hypersensitivity reaction, this case report emphasizes the need for caution when initiating MDT or dapsone therapy. It is also suggested that any patient on MDT or dapsone needs to be referred immediately to a dermatologist or internist if the patient develops a skin rash during the first 2 months of treatment.
Topics: Adolescent; Dapsone; Drug Hypersensitivity; Humans; Leprostatic Agents; Leprosy, Lepromatous; Male; Philippines
PubMed: 8637384
DOI: 10.5935/0305-7518.19950034 -
International Journal of Pediatric... Aug 1995Dapsone is used to treat several systemic inflammatory diseases, many of which have head and neck manifestations, such as leprosy, systemic lupus erythematosus,...
Dapsone is used to treat several systemic inflammatory diseases, many of which have head and neck manifestations, such as leprosy, systemic lupus erythematosus, rhinosporidiosis, relapsing polychondritis, dermatitis herpetiformis, pemphigus vulgaris and bullous pemphigoid. It has also been recently used prophylactically alone or in combination against malaria and in AIDS patients against Pneumocystis carinii infections. This is significant to the otolaryngologist-head and neck surgeon since approximately 40% of AIDS patients will have head and neck manifestations. Thus, the likelihood that otolaryngologists will be treating patients who are taking dapsone regularly is significant. We present a case of a 16-year-old female who presented with a presumptive diagnosis of discoid lupus for biopsy confirmation of her disease. Induction of general anesthesia was complicated by methemoglobinemia, an uncommon side effect of dapsone. We will discuss recognition and prevention of this side effect, its potential anesthetic implications, complications and treatment.
Topics: Adolescent; Anesthesia, General; Dapsone; Female; Humans; Lupus Erythematosus, Discoid; Methemoglobinemia
PubMed: 7558644
DOI: 10.1016/0165-5876(95)01186-f -
Antimicrobial Agents and Chemotherapy Nov 1999Although dapsone is a commonly used alternative agent for prophylaxis against Pneumocystis carinii pneumonia in children intolerant to trimethoprim-sulfamethoxazole,... (Clinical Trial)
Clinical Trial
Although dapsone is a commonly used alternative agent for prophylaxis against Pneumocystis carinii pneumonia in children intolerant to trimethoprim-sulfamethoxazole, there are few data that describe dapsone pharmacokinetics in children. We studied dapsone pharmacokinetics in 30 children (median age, 2.8 years; age range, 0. 3 to 12 years) receiving a new proprietary liquid preparation by three dosing regimens (1 mg/kg of body weight daily, 2 mg/kg daily, or 4 mg/kg weekly). Dosing of children with 2 mg/kg daily or 4 mg/kg weekly resulted in peak concentrations equivalent to those reached in adults receiving 100-mg tablets daily. For the entire population, the median half-life was 22.2 h (range, 7.1 to 40.3 h), the median oral clearance was 0.0365 liter/kg/h (range, 0.0104 to 0.1021 liter/kg/h), and the median oral apparent volume of distribution was 1.13 liters/kg (range, 0.50 to 2.32 liters/kg). The median dapsone oral clearance was significantly increased in those infants less than 2 years of age compared to the oral clearance in those over 2 years of age (0.0484 versus 0.0278 liter/kg/h; P = 0.011). These data suggest that absorption of this liquid preparation is adequate and that the concentrations in the sera of children receiving 2 mg/kg daily or 4 mg/kg weekly are equivalent to those seen in adults receiving standard dapsone dosing. Dapsone oral clearance appears to be increased in children under 2 years of age.
Topics: Adolescent; Anti-Infective Agents; Child; Child, Preschool; Chromatography, High Pressure Liquid; Dapsone; Female; HIV Infections; Humans; Infant; Male; Pneumonia, Pneumocystis
PubMed: 10543733
DOI: 10.1128/AAC.43.11.2586 -
Prescrire International Dec 2002
Topics: Chemical and Drug Induced Liver Injury; Dapsone; Drug Hypersensitivity; France; Health Care Surveys; Hematologic Diseases; Humans; Leprosy; Mental Disorders; Skin Diseases
PubMed: 12472098
DOI: No ID Found -
Pharmacology 1981Concentrations of dapsone (DDS) and its metabolite, monoacetyl dapsone (MADDS) were measured in plasma and saliva samples collected concurrently from volunteers...
Concentrations of dapsone (DDS) and its metabolite, monoacetyl dapsone (MADDS) were measured in plasma and saliva samples collected concurrently from volunteers receiving a 50-mg oral dose of DDS. A liquid chromatographic technique was employed to separate the compounds from each other and from endogenous materials. Fluorescence detection provided limited sensitivities to 0.1 ng/ml of sample. Saliva levels of DDS were consistently 15-20% of the plasma levels of DDS during the study period, which ranged from 4 to 48 h. Decay rates for DDS from saliva and plasma were nearly identical. In 4-hour samples of plasma subjected to equilibrium dialysis, we found amounts of DDS in the dialysates nearly identical to levels found in saliva collected at that time. Saliva levels of MADDS ranged from 0.8 to 2.6% of their plasma levels at all times. Decay rates of MADDS from the two fluids were nearly identical and saliva levels of MADDS in 4-hour samples were nearly identical to levels found in paired plasma dialysates. Nevertheless, levels of MADDS were so low that a reliable definition of the subjects' acetylator phenotype from levels of MADDS in saliva only was impossible.
Topics: Acetylation; Adult; Dapsone; Female; Half-Life; Humans; Male; Saliva
PubMed: 7208598
DOI: 10.1159/000137486 -
Ophthalmology Nov 1994Dapsone is used widely in treating ocular cicatricial pemphigoid, leprosy, and dermatologic disorders. Hemolysis is a well-known complication of dapsone therapy. Rarely,...
BACKGROUND
Dapsone is used widely in treating ocular cicatricial pemphigoid, leprosy, and dermatologic disorders. Hemolysis is a well-known complication of dapsone therapy. Rarely, neutropenia or agranulocytosis may occur, resulting in up to a 50% mortality rate. To the authors' knowledge, agranulocytosis has not been reported in patients treated with dapsone for ocular cicatricial pemphigoid.
METHODS
The authors report two cases of dapsone-induced neutropenia with bone marrow suppression in patients with ocular cicatricial pemphigoid.
RESULTS
Neutropenia was detected on routine laboratory examination 8 and 10 weeks after initiating dapsone therapy. Bone marrow biopsy showed acellular or hypocellular marrow. Leukocyte count returned to baseline value after cessation of dapsone.
CONCLUSION
Patients with ocular cicatricial pemphigoid who were treated with dapsone are at increased risk for agranulocytosis. Dapsone-induced neutropenia may not be a dose-dependent phenomenon. The authors indicate that there is a need for routine monitoring of leukocyte counts, especially 8 to 10 weeks after initiating therapy. Signs or symptoms of infection require immediate investigation.
Topics: Aged; Dapsone; Eye Diseases; Humans; Male; Neutropenia; Pemphigoid, Benign Mucous Membrane; Time Factors
PubMed: 7800360
DOI: 10.1016/s0161-6420(94)31098-0