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PubMed1975

The disposition of dapsone and monoacetyldapsone in the dog (38516).

Four female dogs receiving 1.0 mg dapsone (DDS)/kg iv exhibited logarithmic decline of plasma levels of DDS with a mean half-time of disappearance (T-1/2 of 11.7 hr. No evidence of acetylation of DDS to monoacetyl DDS (MADDS) was found. An equimolar dose of MADDS was deacetylated slowly to DDS by the same dogs. The mean T 1/2 of MADDS was 6.5 hr, significantly less than that of DDS. In 2-hr plasma samples after these doses of drugs, protein-binding of DDS and MADDS averaged 71 and 84%, respectively. Tests of protein-binding of the two drugs in vitro confirmed the observations in vivo.

Acetylation↗
PubMed1997

Dapsone maculopathy.

After the injection of about 10 gm of dapsone, a 38-year-old male showed a whitish-yellow patch in the macular region of both eyes, with decreased visual acuity of the counting finger in the right and 0.04 in the left eye. Two weeks after the start of systemic steroid therapy the patch disappeared, and on follow-up at 11 months, visual acuity was 0.02 in the right and 0.08 in the left eye, with macular degeneration and foveal nonperfusion. This retinal damage seems to be ischemic in origin and to be caused by a combination of acute severe peripheral hypoxemia and the vascular obstructive effect of red cell fragmentation resulting from massive hemolysis.

Adult↗
PubMed1975

Polymorphic acetylation of the antibacterials, sulfamethazine and dapsone, in South Indian subjects.

A group of South Indian subjects was studied for their capacities to acetylate sulfamethazine (SMZ) and dapsone (DDS) and to clear DDS from the circulation. An apparent trimodal distribution of acetylator phenotypes was found in 49 subjects (51% slow, 12% intermediate, and 37% rapid acetylators) from measurements of the percentage acetylation of SMZ in 6-hour plasma samples after administration of 10 mg SMZ/kg. The intermediate phenotype was not discernible from either the percentage acetylation of SMZ in urine (collected concurrently with the plasma after SMZ) or that of DDS in plasma after the ingestion of 50 mg DDS by the same subjects. The latter two measurements yielded a bimodal distribution of 59% slow and 41% rapid acetylators, nearly identical to earlier reported distributions of isoniazid inactivator phenotypes in larger numbers of South Indian tuberculosis patients. In the current group, acetylation of DDS and SMZ was positively correlated. The half-time of disappearance (T 1/2) of DDS, an expression of the rate of clearance from the plasma, ranged from 13 to 40 hours. No correlation was found between the subject's capacity to acetylate DDS and the T 1/2 value for DDS. These results were generally consistent with earlier observations made during similar studies of American and Filipino subjects.

Acetylation↗
PubMed1989

Primary dapsone chemoprophylaxis for Pneumocystis carinii pneumonia in immunocompromised patients infected with the human immunodeficiency virus.

During a 12-month period from August 1, 1986 to July 31, 1987, a study of primary chemoprophylaxis with dapsone for Pneumocystis carinii pneumonia was undertaken in immunodeficient patients who were infected with the human immunodeficiency virus. One attack of P. carinii pneumonia occurred among 16 patients who received chemoprophylaxis immediately that a T-helper (CD4) lymphocyte count of less than 0.2 x 10(9)/L was recorded compared with 16 attacks in the historical control group of 46 similar patients who did not receive chemoprophylaxis (log-rank test, chi 2(1) = 3.72; P = 0.05).

AIDS-Related Complex↗
PubMed1989

Evaluation of Mycobacterium leprae antigens in the serological monitoring of a clofazimine-based chemotherapeutic study of dapsone resistant lepromatous leprosy patients in Cebu, Philippines.

Thirty-one dapsone resistant lepromatous leprosy patients receiving clofazimine based therapy were serologically monitored throughout their 5-year period of treatment. Sequentially collected sera were used to examine 4 Mycobacterium leprae antigens to evaluate their usefulness in ELISA's for monitoring the progress of their therapy. The ELISA results were compared with decline in bacterial load over the treatment period and with duration of treatment. In addition the ELISA's were compared with each other. The ELISA's based on the measurement of IgM antibodies to the two neoglycoproteins (NDO and NTO) representing the phenolic glycolipid antigen of M. leprae were found to be the most effective with regard to monitoring treatment. A whole M. leprae based ELISA was less efficient in monitoring treatment because it failed to measure antibodies in 5 out of 31 patients. The ELISA-inhibition test based on the detection of antibodies to a species-specific epitope on the 36 K antigen of M. leprae was less suitable because of persistent reactivity during therapy.

Adult↗
PubMed1989

Evaluation of Mycobacterium leprae antigens in the monitoring of a dapsone-based chemotherapy of previously untreated lepromatous patients in Cebu, Philippines.

Thirty-five previously untreated lepromatous patients receiving dapsone-based therapy were monitored throughout their 5-year period of treatment by serology and by pathology. Sequentially collected sera were used to evaluate the usefulness of four Mycobacterium leprae antigens as used in ELISA to monitor the progress of their therapy. ELISA results were compared with each other and with bacterial load over the treatment period and with duration of treatment. The ELISAs, based on the measurement of IgM antibody reactivity to the two neoglycoproteins (NDO and NTO) representing the phenolic glycolipid antigen of M. leprae, were found to be the most effective in monitoring treatment. A whole M. leprae based ELISA was less efficient in monitoring treatment because it failed to measure antibodies in 8 out of 35 patients and because it provided consistently lower values than either NTO or NDO. The ELISA-inhibition test based on the detection of antibodies to a species-specific epitope on the 36 K antigen of M. leprae was less suitable because of persistent reactivity during therapy, consequently resulting in no significant correlation with ELISA reactivities to NTO or NDO.

Antibodies, Bacterial↗
PubMed1991

A controlled therapeutic trial in paucibacillary leprosy comparing a single dose of rifampicin with a single dose of rifampicin followed by one year of daily dapsone. The Collaborative Study Group for the Treatment of Leprosy in Zaire.

The cure rates of two treatment regimens in PB leprosy were compared in a prospective randomized trial: treatment U consisting of a single dose of rifampicin 40 mg/K bodyweight, and treatment A of rifampicin 1500 mg in a single dose, followed by one year of daily dapsone 100 mg. In patients with a BI = 0, the cure rates evaluated on the basis of histopathology of skin biopsies, were identical for the two regimens but in patients with a BI = 1, cure and relapse rates were unacceptable. For this reason and particularly the need to separate patients on the basis of the BI in skin biopsies, the single dose regimen does not appear to be suited for wide-scale application.

Dapsone↗
PubMed1991

Risk of relapse among non-lepromatous patients released from treatment after dapsone monotherapy.

Information on 14,625 non-lepromatous patients released from treatment after dapsone monotherapy and followed up to a maximum of 15 years at the ILEP project. Dharmapuri, India, was analysed to study the pattern of relapses. The overall relapse rate was 5/1000 person years. Males had a higher relapse rate than females. The risk of relapse increased with age, number of lesions and duration of treatment. The risk for relapse remained constant over several years after release from treatment. Even though the absolute risk for relapse after MDT may be different, the pattern of relapses and the factors affecting it may be similar to what has been shown in this study.

Adolescent↗
PubMedDate not supplied

Dapsone resistance does not appear to be associated with a mutation in the dihydropteroate synthase-2 gene of Mycobacterium leprae.

Evidence suggests that resistance to dapsone (DDS) in Mycobacterium leprae is related to the enzyme dihydropteroate synthase (DHPS). Two M. leprae genes (folP-1 and folP-2) encoding DHPS-1 and DHPS-2, respectively, have been identified through the M. leprae genome project. We have studied DDS-susceptible and resistant strains of M. leprae to determine whether the DDS-resistant phenotype is associated with a mutation(s) in folP-2 and to establish the number of genomic copies of the gene encoding DHPS-2 (folP-2). RFLP analysis of genomic DNA from DDS-susceptible and resistant strains of M. leprae exhibited a unique 4.2 kb restriction fragment consistent with a single genomic copy of folP-2 in both phenotypes. DNA encoding folP-2 was amplified by PCR and sequenced from two susceptible and two resistant strains of M. leprae. The folP-2 sequences from these strains were identical indicating that resistance to DDS was not associated with mutation(s) in the gene encoding DHPS-2.

Amino Acid Sequence↗
PubMed2000

Dapsone resistance in Mycobacterium leprae.

The folP1 gene of Mycobacterium leprae, which encodes dihydropteroate synthase (DHPS), was studied for the presence of mutations associated with resistance to dapsone (DDS). When the folP1 of several DDS-resistant clinical isolates of M. leprae were sequenced, two missense mutations were identified. One mutation occurred at codon 53, substituting isoleucine for threonine in DHPS-1, and a second mutation occurred in codon 55, substituting arginine for proline. DNA sequencing of strains of M. leprae resistant to 0.01 g% DDS in the mouse diet revealed that 13 of 14 strains contained either the 53 or 55 folP1 mutation. None of the susceptible strains and only one of five strains resistant to 0.001 g% DDS revealed a mutation in folP1, suggesting that only high-level DDS resistance is associated with the mutations identified in folP1. Development and application of simple molecular tests to assess drug-related mutations in M. leprae could establish current levels of drug resistance in leprosy as a reference point for future monitoring of drug resistance at the global level.

Dapsone↗
PubMed2000

A Mycobacterium leprae isolate resistant to dapsone, rifampin, ofloxacin and sparfloxacin.

Mycobacterium leprae were isolated from a Japanese patient, and susceptibility to antileprosy drugs was examined by the mouse foot pad method. The isolate was susceptible to clofazimine and clarithromycin, and resistant to dapsone, rifampin, ofloxacin and sparfloxacin. Mutations were identified in the genes associated with resistance to these drugs. The risk of the emergence of leprosy with multidrug resistance is emphasized.

Animals↗
PubMed2001

[Respiratory insufficiency caused by dapsone-induced methemoglobinemia].

We present a case of pneumonia and dapsone-induced methaemoglobinaemia. Methaemoglobinaemia leads to impaired delivery of oxygen to tissue. In our patient we observed that methaemoglobin interferes with the accuracy of pulse oximeter data. The patient was successfully treated with methylene blue, which converts methaemoglobin back to haemoglobin.

Anti-Infective Agents↗
PubMedDate not supplied

Dapsone a new diazotizing reagent for the spectrophotometric determination of nitrite in waste and natural water samples.

A new diazotizing reagent for the spectrophotometric determination of nitrite is described. The method is based on diazotization-coupling reaction between dapsone and phloroglucinol in hydrochloric acid medium. The reactions were conducted at room temperature, the molor absorptivity at 425 nm is 4.28 x 10(4) l mol-1cm-1 and was stable for 50 h. Beer's law was obeyed in the nitrite range of 0.008-1.0 microgram ml-1. Tolerance limits were tested for 33 species. The method has been found to be applicable for the determination of nitrite in natural and wastewater.

Anti-Infective Agents↗
PubMed2002

Dapsone.

Dapsone (4,4'-diaminodiphenylsulfone, DDS) was synthesized a century ago and continues to be a powerful therapeutic tool in many skin diseases. We have tried to retrieve and present the available knowledge and relevant information on this old but still very useful drug with the hope of encouraging and guiding practicing dermatologists to adapt it for various indications. Our objective is to familiarize the clinician with how this agent works, in what disease states it is effective, how to administer it, what adverse effects may occur, and how to monitor the patient receiving this drug.

Animals↗
PubMedDate not supplied

Generalized lichen planus in childhood: is dapsone an effective treatment modality?

Childhood lichen planus is generally atypical in appearance, prolonged in duration and resistant to therapy. Moreover, the risk in administration of systemic drugs because of several adverse effects limits their use and effective therapy remains a problem in this age group. We report a case of generalized lichen planus in a nine-year-old boy with oral mucosa and nail involvement who was treated with dapsone.

Anti-Infective Agents↗
PubMed1992

Does isoniazid increase the hepatotoxicity of the combination prothionamide-dapsone? Isoprodian Study Group.

In order to assess the potential additive liver toxicity of isoniazid to that of a thioamide-containing treatment, a prospective, randomized, double-blind trial of 24 weeks' duration involving 772 adult patients was conducted in four leprosy centers--two in India, one in Madagascar, and one in the Ivory Coast. Patients with multibacillary leprosy were given daily 100 mg dapsone (DDS) and 350 mg prothionamide (PTH) plus monthly 600 mg rifampin (RMP) in combination either with 350 mg isoniazid (INH) or with a placebo. After clinical and laboratory (including HBs-Ag testing) examinations on admission, the side effects (especially gastrointestinal disturbances and liver toxicity) were assessed at regular intervals during treatment by laboratory testing (aminotransferases, bilirubin, alkaline phosphatase) and by recording spontaneous complaints. Analysis of the frequency and seriousness of the side effects was made before breaking the code (with or without INH). Although 10% of the patients had liver toxicity leading to stopping treatment, no significant difference in the occurrence of side effects was observed between patients treated with or without INH. Most (75%) of the observed side effects occurred during the first 4 weeks of treatment, and the time of their onset was not related to INH. Body weight and age were factors related to the frequency of side effects [the higher the body weight, the lesser the rate of side effects (p = 0.03)] and the rate of serious side effects increased with age (p = 0.02). But, again, the frequency of the side effects was not related to INH administration. Therefore, from the present study it can be concluded that INH does not increase the toxicity of the thioamide-containing treatment.

Adolescent↗
PubMed1992

Dapsone in cutaneous lesions of SLE: an open study.

This short report describes a possible beneficial effect of dapsone in the treatment of chronic unresponsive muco-cutaneous lesions of systemic lupus erythematosus (SLE) without any serious side effects.

Adult↗
PubMed1992

Chemoprophylaxis against malaria in Papua New Guinea: a trial of amodiaquine and a combination of dapsone and pyrimethamine.

A placebo-controlled chemoprophylaxis trial was carried out in 1980 in 318 semi-immune school children in the Madang area of Papua New Guinea, where there was a high prevalence of strains of Plasmodium falciparum resistant to 4-aminoquinolines. Since prophylaxis with amodiaquine at 5 mg/kg weekly had failed, amodiaquine at a dose of 10mg/kg weekly and Maloprim (half a tablet or one tablet depending on body weight, which gave ranges of dapsone of 1.7-3.3mg/kg and pyrimethamine 0.2-0.4 mg/kg) weekly were tried. Neither regimen was completely successful in preventing parasitaemia, though after 13 weeks of prophylaxis the slide positivity rate was 16% for the amodiaquine group and 2% for the Maloprim group, which was in each case significantly lower than the normal baseline rate in the controls of 42%. Amodiaquine was completely successful in suppressing Plasmodium vivax infections. Breakthrough parasitaemia occurred, with either P. falciparum or P. vivax, in 5% of subjects on Maloprim at some time during the 13-week period of prophylaxis. Significantly more children in both the amodiaquine and Maloprim groups than in the placebo group showed a reduction in spleen size. All groups showed an unexplained fall in haemoglobin level over the study period but the fall was significantly less in both the prophylaxis groups. There was no adverse effect on white cell counts by either drug regimen. Chemoprophylaxis as a component of an integrated malaria control program should not be overlooked, provided that compliance can be maintained. However, in this particular case the principal purpose of the study had been to evaluate the proposed chemoprophylactic regimens in school children before embarking on an intervention study in young children. As a result of this study it was decided not to go ahead with the chemoprophylactic intervention in young children but to adopt an approach based on early presumptive treatment.

Antimalarials↗