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PubMedDate not supplied

Anticonvulsive effect of dapsone (4,4'-diaminodiphenyl sulfone) on amygdala-kindled seizures in rats and cats.

Dapsone (4,4'-diaminodiphenyl sulfone; DDS), an established anti-leprosy drug, showed anticonvulsive effects in the amygdaloid kindling model of epilepsy. Single doses of the drug in rats (6.25-12.5 mg/kg, i.p.) suppressed the kindled seizures in a dose-dependent manner without overt behavioral toxicity. With repeated oral administration in cats, relatively higher initial doses (13-23 mg/kg) were required to obtain seizure suppression, and neurotoxic signs occurred within a few days with serum drug levels of approximately 20 micrograms/ml. Although dapsone showed anticonvulsive effects in both animal species, the effective serum levels overlapped the toxic levels reported in the clinical treatment of leprosy. In the majority of the cats, however, seizure suppression was maintained even after the discontinuation of dapsone with lower serum levels than those observed at the beginning of the seizure suppression. Therefore, dapsone would be useful as an antiepileptic drug only when long-term anticonvulsive efficacy is demonstrated using smaller doses comparable to those used in the treatment of leprosy.

Amygdala↗
PubMed1997

Ex vivo antimalarial activity of proguanil combined with dapsone against cycloguanil-resistant Plasmodium falciparum isolates.

The ex vivo antimalarial activity of plasma samples obtained from 20 healthy Caucasian volunteers following daily proguanil (200 mg) plus dapsone (8 mg) for malaria chemoprophylaxis inhibited five cycloguanil-resistant Thai isolates of Plasmodium falciparum. All volunteers were phenotyped as extensive metabolisers (EMs) of proguanil. Three of the five isolates were obtained from Thai soldiers who had failed malaria prophylaxis on daily proguanil (200 mg) plus dapsone (4.0 or 12.5 mg). The Thai soldiers were also classified as EMs, but had relatively lower plasma cycloguanil concentrations compared to values reported in the literature for Caucasians and black Kenyans. Although the high level of parasite resistance to cycloguanil was the most likely explanation for the Thai soldiers failing prophylaxis on proguanil plus dapsone, their low cycloguanil concentrations may have also contributed to their lack of protection. However, in areas where parasites are more susceptible to cycloguanil, such as in certain regions of Africa, proguanil plus dapsone may still be an effective chemoprophylactic drug combination.

Animals↗
PubMed1997

Haematological and biochemical alterations in leprosy patients already treated with dapsone and MDT.

Dapsone (DDS) is useful in the treatment of a number of inflammatory conditions which are characterized by neutrophil infiltration. It is the drug of choice for the treatment of leprosy and prophylaxis of malaria. Haematological side effects of methaemoglobinaemia and haemolysis have been long recognized. However, the frequency and severity of these side effects in patients already treated with DDS as a single drug or as part of a multidrug therapy (MDT) have not been well documented. We report herein an investigation of the effect of dapsone long-term treatment on the haematological and biochemical alterations in leprosy patients undergoing dapsone as a single drug (DDS group) or as part of a multidrug therapy in combination with rifampin and clofazimine (MDT group). Methaemoglobinaemia and haemolytic anaemia were the principal side effects observed. Reticulocytes were found to be elevated (> 1.5%) in 90% of the patients. Heinz bodies were also detected (6.6% of the patients). The osmotic fragility test showed a reduction in cell resistance and in the evaluation of white cells a severe eosinophilia was found. Hepatic, pancreatic and renal evaluation by the determination of biochemical parameters showed rare and occasional changes of no apparent clinical significance. We conclude that haematological side effects of dapsone are significant even at doses currently used to treat leprosy (100 mg/day) and that rifampin and clofazimine do not increase the incidence of these effects during long-term treatment.

Clofazimine↗
PubMed1982

Treatment of cicatricial (benign mucous membrane) pemphigoid with dapsone.

Treatment of cicatricial pemphigoid is a problem because patients afflicted are elderly, the disease is chronic, systemic agents required for control are potentially toxic (particularly to older patients), and the disease is often in an advanced stage when the diagnosis is established and requires aggressive therapy for control. We selected dapsone as an alternative anti-inflammatory agent because it has provided control in a subset of patients with bullous pemphigoid, five of six who had oral lesions. Twenty-four patients with cicatricial pemphigoid were treated with dapsone. Twenty (83.3%) had partial or complete control with mild to no inflammatory activity. Control was obtained within 4 weeks in eleven of the twenty patients. The use of dapsone was discontinued in two patients because it failed to control their disease and in four patients (two with control) because of drug-related side effects. Cicatricial pemphigoid may be added to the list of dapsone-responsive dermatoses.

Adult↗
PubMed1994

Dapsone or electric shock therapy of brown recluse spider envenomation?

STUDY OBJECTIVES: We tested the null hypothesis that no outcome differences exist among the treatment groups of animals with brown recluse spider envenomations. STUDY DESIGN: A prospective, placebo-controlled, experimental trial. Hartley guinea pigs were randomized into the following treatment groups: dapsone, Parali/azer stun gun, Guardian stun gun, and control. INTERVENTIONS: Brown recluse spider skin lesions were induced with intradermal injections of 30 micrograms spider venom and were treated beginning 16 hours after inoculation. Shock regimens consisted of four cross shocks of 1-second duration on anesthetized animals. Oral dapsone treatment was 0.7 mg/kg twice daily for 3 days. Lesion areas were measured daily for 3 days. RESULTS: The dapsone therapy group demonstrated significantly less induration and necrosis (P < .05) than that shown by the other three groups 72 hours after envenomation. CONCLUSION: Dapsone therapy is more effective than either electric shock or no therapy for brown recluse spider envenomation in the guinea pig model.

Analysis of Variance↗
PubMed1995

Therapy of brown spider envenomation: a controlled trial of hyperbaric oxygen, dapsone, and cyproheptadine.

STUDY OBJECTIVE: To determine whether hyperbaric oxygen (HBO), dapsone, or cyproheptadine decreases the severity of skin lesions resulting from experimental Loxosceles envenomation. DESIGN: Randomized, blinded, controlled study. SETTING: Animal care facility. INTERVENTIONS: We used New Zealand white rabbits. All groups received 20 micrograms of pooled L deserta venom intradermally. Our control group received 4 ml of a 5% ethanol solution by oral gavage every 12 hours for 4 days. The HBO group received hyperbaric oxygen at 2.5 ATA for 65 minutes every 12 hours for 2 days, plus 5% ethanol solution for 4 days. The dapsone group received dapsone 1.1 mg/kg in 5% ethanol by gavage every 12 hours for 4 days. The cyproheptadine group received cyproheptadine .125 mg/kg in 5% ethanol by gavage every 12 hours for 4 days. RESULTS: Total lesion size and ulcer size were followed for 10 days. The lesions were then excised, examined microscopically, and ranked by the severity of the histopathology. The groups did not differ significantly with respect to lesion size, ulcer size, or histopathologic ranking. CONCLUSION: Given the negative result in this study with adequate power to detect meaningful treatment benefits, we cannot recommend hyperbaric oxygen, dapsone, or cyproheptadine in the treatment of Loxosceles envenomation.

Animals↗
PubMed1997

Structural basis for the haemotoxicity of dapsone: the importance of the sulphonyl group.

The structural basis of dapsone (4,4'-diaminodiphenyl sulphone) haemotoxicity has been determined by investigation of the in vitro bioactivation of a series of 4-substituted arylamines. In the presence of rat liver microsomes, dapsone (100 microM) was the most potent former of methaemoglobin in human erythrocytes (44.8 +/- 6.7%). Substitution of the sulphone group with sulphur (11.6 +/- 1.4% methaemoglobin), oxygen (4.5 +/- 1.1%), nitrogen (0.0 +/- 3.2%), carbon (13.6 +/- 0.8%) or a keto group (34.0 +/- 6.1%) resulted in a decrease in methaemoglobin formation. Only one compound, 4,4'-diaminodiphenylamine, generated significant (P < 0.001) amounts of methaemoglobin (25.6 +/- 2.5%) in the absence of NADPH. To assess further the role of the 4-substituent in methaemoglobinaemia, the toxicity of a series of 4-substituted aniline derivatives was also studied. Of the anilines studied, 4-nitroaniline caused the most methaemoglobin (36.5 +/- 8.0%), whilst aniline caused the least (0.3 +/- 0.5%). Overall, there was a significant correlation (r2 = 0.83) between the haemotoxicity and the Hammett constant, sigma(p), suggesting that it is the electron-withdrawing properties of the substituent that influence the methaemoglobin formation. In the presence of microsomes prepared from two human livers, dapsone was the most haemotoxic bis arylamine, whereas 4-iodoaniline was the most potent methaemoglobin former (60.6 and 73.6%) and aniline the least potent (1.1 and 2.4%). As a whole, these results indicate that the sulphonyl group, which is essential for the pharmacological activity of dapsone, is also largely responsible for the haemotoxicity seen with this drug.

Animals↗
PubMed2002

In vivo activity of epiroprim, a dihydrofolate reductase inhibitor, singly and in combination with dapsone, against Mycobacterium leprae.

The antimicrobial effects of a new dihydrofolate reductase inhibitor, epiroprim, either singly or in combination with dapsone against Mycobacterium leprae, were evaluated in vivo using a mouse footpad model. When fed to mice at concentration of 0.05% in diet, epiroprim completely inhibited the growth of both dapsone-sensitive and dapsone-resistant strains of M. leprae in the footpads of mice and the effects were bactericidal. To achieve similar effects, the concentration of dapsone in the diet had to be 0.0005 and 0.01%, respectively. When used in combination, the concentrations of the drugs in the diet could be lowered by 50-80% and still achieve bactericidal effects. The data support the earlier results on in vitro studies and suggest the use of epiroprim in the multidrug regimen in the treatment of leprosy.

Administration, Oral↗
PubMed1999

A retrospective study of the management of oral mucous membrane pemphigoid with dapsone.

OBJECTIVE: The purpose of this retrospective study was to investigate the efficacy of dapsone therapy in the management of mucous membrane pemphigoid. STUDY DESIGN: The charts of 29 patients who had been diagnosed with mucous membrane pemphigoid by means of routine histologic analysis and direct immunofluorescence were reviewed. The oral features were graded according to severity of disease from 1 to 3. Each patient was assigned to one of 4 groups according to his or her response to therapy. RESULTS: Nine patients were treated successfully with topical corticosteroids alone. Eleven patients with moderate to severe disease who were treated initially with topical steroids showed minimal improvement; after dapsone was added, 7 of the 11 had total resolution of their lesions and 4 had greater than 75% improvement. Two patients had to discontinue dapsone because of side effects. CONCLUSIONS: In this group of 20 patients with moderate to severe mucous membrane pemphigoid, the use of dapsone in combination with topical corticosteroids caused greater than 75% resolution of oral lesions in all patients studied.

Administration, Topical↗
PubMed2003

A near fatal case of the dapsone hypersensitivity syndrome in a patient with urticarial vasculitis.

Dapsone (4,4'-diaminodiphenyl sulphone) is used for a variety of dermatological conditions including immunobullous diseases and urticarial vasculitis. Side-effects are common and include lethargy, headaches, methaemoglobinaemia and haemolysis. Severe adverse effects are rare but the dapsone hypersensitivity syndrome is well recognized. Symptoms include fever, haemolytic anaemia, lymphocytosis and hepatitis. We report a near fatal case of the dapsone hypersensitivity syndrome in a patient with urticarial vasculitis. This diagnosis should be remembered in any patient who becomes unwell whilst taking dapsone.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMedDate not supplied

Dapsone-induced methemoglobinemia in pediatric oncology patients: case examples.

Over the last 25 years, significant advances have been made in supportive care of the immunocompromised patient. One significant advance is the use of trimethoprim-sulfamethoxazole (TMP-SMZ) in the prevention of Pneumocystic carinii pneumonia (PCP). Although TMP-SMZ remains the drug of choice for PCP prophylaxis, children who develop or have a history of adverse reactions must be prescribed an alternative treatment. In these instances, medications such as dapsone, aerosolized pentamidine, or atovaquone are prescribed. This report discusses four children with sulfa allergy who were prescribed dapsone and later developed methemoglobinemia. Although methemoglobinemia is associated with dapsone, there was no reference found regarding this link in the pediatric oncology literature. The purpose of these clinical examples is to alert the pediatric nurse and advanced practitioner to the association of dapsone and methemoglobinemia.

Adolescent↗
PubMed1994

Adverse reactions to dapsone in persons infected with human immunodeficiency virus.

Dapsone is used in prophylaxis for and treatment of Pneumocystis carinii pneumonia. We present a case of Stevens-Johnson syndrome that was likely induced by administration of dapsone. A review of charts at the HIV Treatment Center of Northwestern University (Chicago) revealed that 40.3% of patients treated with trimethoprim-sulfamethoxazole could not tolerate the medication, while 25.2% of those treated with dapsone were intolerant of the drug. We also found a higher rate of adverse reactions to dapsone among patients with prior intolerance to trimethoprim-sulfamethoxazole than among patients without such a history; however, the difference was not significant.

Acquired Immunodeficiency Syndrome↗
PubMed1986

The effect of clofazimine on the pharmacokinetics of rifampicin and dapsone in leprosy.

Fifteen untreated leprosy patients were given rifampicin and dapsone for seven days, and then rifampicin, dapsone and clofazimine for seven days. Concentrations of rifampicin and dapsone were estimated in timed plasma specimens and in 24 h urine specimens on days 7 and 14. No significant differences in the pharmacokinetics of rifampicin and dapsone were observed between the two occasions of sampling.

Clofazimine↗
PubMed1985

Brown recluse spider bites. A comparison of early surgical excision versus dapsone and delayed surgical excision.

In a prospective study, 31 patients with brown recluse spider bites were treated by either immediate surgical excision or with the leukocyte inhibitor, dapsone, followed by delayed surgical excision. Patients were matched for age, gender, and lesion size and were excluded if the typical history and physical findings were not present. In patients treated with immediate surgical excision (N = 14), delayed wound healing (N = 5) and objectional scarring (N = 7) were common complications. However, pretreatment treatment with dapsone reduced the incidence of wound complications (N = 1) and objectional scarring (N = 1) (p less than 0.05), while reducing the need for surgical excision (N = 1). There were no severe drug reactions due to dapsone, although one patient had persistent G.I. upset. Pretreatment with dapsone not only reduced surgical complications but also improved the outcome of patients bitten by the brown recluse spider.

Adolescent↗
PubMed1990

Low-dose dapsone prophylaxis of Pneumocystis carinii pneumonia in AIDS and AIDS-related complex.

The efficacy, toxicity and cost of orally administered dapsone (50-100 mg/day) for prophylaxis of Pneumocystis carinii pneumonia (PCP) were evaluated in 30 patients with AIDS or AIDS-related complex (ARC). Six patients received primary and 24 secondary prophylaxis. Ten patients received a maximum dose of 100 mg/day and 20 a maximum of 50 mg/day for a median duration of 19 weeks; 22 of the 30 patients continue to receive prophylaxis as of May 1989. Four patients have died, none of pneumocystis infection. One patient with AIDS suffered a mild relapse while receiving 50 mg/day. Hematologic toxicity was mild and could not be definitively attributed to dapsone therapy; rash due to dapsone was documented in two patients. A review of 33 patients at our institution with a history of PCP who received no prophylaxis demonstrated seven relapses, three of which were fatal. Cost analysis revealed a significant advantage for oral dapsone over aerosolized pentamidine.

AIDS-Related Complex↗
PubMed1993

Utility of dapsone for prophylaxis of Pneumocystis carinii pneumonia in trimethoprim-sulfamethoxazole-intolerant, HIV-infected individuals.

OBJECTIVE: To determine the safety and efficacy of 100 mg dapsone three times weekly for Pneumocystis carinii pneumonia (PCP) prophylaxis in HIV-infected, trimethoprim-sulfamethoxazole (TMP-SMX)-intolerant patients. DESIGN: Retrospective chart review of patients followed-up to 22 May 1992. SETTING: Infectious diseases outpatient clinic of a tertiary care center in suburban New York City. PATIENTS: Twenty-three HIV-infected patients requiring PCP prophylaxis with documented intolerance to TMP-SMX. MAIN OUTCOME MEASURES: Patients were followed clinically and with laboratory testing at approximately monthly intervals. RESULTS: Dapsone was discontinued in nine (39%) patients because of adverse reactions. All reactions occurred within the first 2 months of treatment. Two (14%) of the remaining 14 patients developed histologically proven PCP over 126 patient-months of follow-up. CONCLUSION: Approximately 40% of TMP-SMX-intolerant HIV-infected individuals are also intolerant of dapsone. Prophylaxis failures may be expected on a dose regimen of 100 mg dapsone three times weekly. More experience with other dose regimens and alternative agents is needed.

AIDS-Related Opportunistic Infections↗
PubMed1984

Acetylator phenotyping: the effect of ethanol on the dapsone test.

In twelve healthy drug-free subjects (six slow acetylators), administration of alcohol (to achieve an ethanol concentration between 650 and 1180 mg 1(-1) ) did not significantly affect the ratio of monoacetyl dapsone (MADS) to dapsone (DDS) 3 h after oral dapsone (100 mg). We conclude that moderate acute ethanol consumption is unlikely to alter the acetylator phenotype measured by the dapsone test.

Acetylation↗
PubMed1990

Bioactivation of dapsone to a cytotoxic metabolite: in vitro use of a novel two compartment system which contains human tissues.

1. A two compartment system, comprising two adjacent teflon chambers separated by a semi-permeable membrane, has been devised with which to investigate the generation of drug metabolites that are toxic to human cells in vitro. 2. Compartment A contained a drug-metabolising system (human liver microsomes +/- NADPH) and compartment B contained target cells (human mononuclear leucocytes). The semi-permeable membrane retained protein (m.w. greater than 10,000) but allowed equilibration (within 1 h) of drug and drug metabolites, during which time cells remained viable. 3. Incubation of dapsone (100 microM) with human microsomal protein (2 mg ml-1) and NADPH (1 mM) in compartment A caused cell death (8.7 +/- 1.8%) in compartment B, which was reduced significantly (P less than 0.05) by the addition of glutathione (500 microM). Dapsone in the absence of NADPH was not cytotoxic. 4. Chemical analysis showed the presence of dapsone hydroxylamine as the only stable metabolite in both compartment A (5.2 +/- 0.4% incubated drug) and compartment B (3.5 +/- 0.5%). 5. Irreversible binding of dapsone to cells was significantly (P less than 0.05) reduced by omission of NADPH (85 +/- 13 pmol/10(6) cells) or addition of glutathione (103 +/- 9) compared with control values (153 +/- 51).

Adult↗