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At least 19 recordsLinked to original sources
PubMed1979

Studies on dapsone induced haemolytic anaemia. I. Methaemoglobin production and G-6-PD activity in correlation with dapsone dosage.

The present study was undertaken on the hypothesis that methaemoglobin production and haemolytic anaemia following dapsone administration could be ascribed to an impairment of glucose-6-phosphate dehydrogenase-enzymatic activity. Analysis of the kinetic parameters of the G-6-PD (Vmax and KM) was performed in ten patients, normal with respect to G-6-PD, suffering from various dermatoses. It was concluded that haemolytic anaemia after dapsone therapy is not due to a functional impairment of the enzyme. The close relationship between dapsone dosage, methaemoglobin production and anaemia make reasonable the hypothesis that a toxic dapsone derivative (DDS-NHOH) could be responsible for the methaemoglobin formation and the haemolytic anaemia.

Anemia, Hemolytic↗
PubMed1979

Determination of plasma concentrations of dapsone, monoacetyl dapsone and pyrimethamine in human subjects dosed with maloprim.

A high-performance liquid chromatographic method was developed to enable dapsone, monoacetyl dapsone and pyrimethamine to be measured simultaneously in plasma samples from volunteers in England and Malaysia who had been dosed with Maloprim. Mean half-lives of 25 and 80 h were calculated for dapsone and pyrimethamine, respectively, but there was wide individual variation. All subjects were found to be classifiable as "slow acetylators".

Adult↗
PubMed1979

The pharmacokinetics of dapsone and acetylated dapsone in serum and saliva.

The concentrations of dapsone (DDS) and its acetylated derivatives (MADDS and DADDS) were determined in the serum and saliva after one oral dose of dapsone until 72 hr. The peak serum concentrations of DDS and MADDS were reached, on average, at 3.8--4.3 hr after the dosage. The amounts of DADDS were negligible. The elimination half-life of the first order kinetics was, on average, at 20--21 hr for both DDS and MADDS. The study group included 6 rapid acetylators and 4 slow acetylators with the mean ratios MADDS/DDS 1.0 and 0.19, respectively. No difference in the pharmacokinetics of DDS or MADDS could be seen between the rapid and slow acetylators. The protein-free fractions of DDS and MADDS were 50 and 41 per cent, respectively, of the total serum concentrations as measured at 8 and 32 hr after the dosage. The salivary concentration of DDS was, on average, 49 per cent of the total serum concentration during the whole study period. The salivary concentration of MADDS was 40 per cent, respectively. The elimination half-life of DDS and MADDS in saliva did not differ from that in serum. Between the salivary and serum protein-free concentrations a strict correlation existed (p less than 0.001). The salivary concentration of dapsone and its monoacetyl derivative reflect the protein-free, active drug in serum.

Acetylation↗
PubMed1977

A comparison of low and conventional dosages of dapsone in the treatment of lepromatous leprosy.

A therapeutic trial using two dosages of Dapsone with a schedule of administration of the drug once a week was undertaken at the Central Leprosy Teaching and Research Institute, Chingleput. Adult males with active lepromatous leprosy who were either previously untreated, or who had no specific treatment for at least three months immediately prior to their inclusion into this study, were the subjects of this trial. Two dosages, viz., 10 mg. per kg. body weight/week, and 3.3 mg. per kg. body weight/week, were employed in this trial. It was found that Dapsone administered orally as a single dose once a week was therapeutically effective in most of the patients, and improvement, clinical or bacteriological, was directly related to the duration of treatment, irrespective of the dosage of Dapsone. Blood levels of Dapsone in these patients were in general commensurate with the dose of the drug in either group. No adverse effects on any of the visceral functions were encountered during the prolonged use of this schedule of treatment with Dapsone.

Dapsone↗
PubMed1977

Dapsone-induced peripheral neuropathy.

Peripheral neuropathy is a rare complication of dapsone therapy. This neuropathy appears primarily to be of the motor type, and recovery occurs on discontinuation of the drug therapy. The patient in this report developed a marked motor deficit as well as a selective marked loss of vibration sense shortly after the initiation of a relatively low dose of dapsone. Recovery was rapid on cessation of the therapy. This patient was found to be a slow acetylator of isoniazid, and therefore is probably a slow acetylator of dapsone. The possible mechanisms of the neurotoxicity of dapsone and the role of altered metabolism are discussed.

Acne Vulgaris↗
PubMed1977

High-speed liquid chromatographic analysis of dapsone and related compounds.

A nonaqueous solvent absorptive support system and an aqueous solvent reversed-phase support liquid chromatographic system for analysis of dapsone and related compounds were investigated. The absorptive support system was more suitable for analysis of dapsone in raw materials, formulations, and tissue residues. The suitability was judged by the relative selectivity, efficiency, precision, and sensitivity of the systems. The adsorptive support system was used for the analysis of trace amounts of raw material impurities and dapsone metabolites. Coupling fluorometric detection to the chromatographic system yielded a 10-pg on-column detection limit for dapsone; the UV detection limit was 250 pg.

Adsorption↗
PubMed1979

Effects of gold, dapsone, and prednisone on serum C-reactive protein and haptoglobin and the erythrocyte sedimentation rate in rheumatoid arthritis.

Sequential measurements of serum C-reactive protein (CRP), serum haptoglobin (Hp), and erythrocyte sedimentation rate (ESR) were made in 209 patients with rheumatoid arthritis (RA); 78 of them were treated with gold, 71 with dapsone, and 60 with prednisone. The results were expressed as proportional changes in the measurements at 28-day intervals after treatment began. The period of study was 140 days. During treatment with gold and dapsone there were statistically significant gradual and progressive falls of similar magnitude in serum CRP and ESR. During treatment with prednisone serum CRP and ESR fell abruptly by 28 days and thereafter altered little. At 140 days prednisone had had the largest proportional effect on both measurements. During gold treatment the fall in serum Hp was similar to that of the ESR. In contrast, prednisone had little effect on Hp levels despite large falls in serum CRP and the ESR. Either prednisone stimulates Hp synthesis or the divergence is an expression of the difference in type of effect between gold and prednisone on RA. The effect of dapsone on serum Hp was large and progressive; it partly reflects haemolysis and, since the haemolysis was not progressive, partly improvement in the RA. The results show the relative efficacy of the drugs and suggest that dapsone may be a useful alternative treatment for RA.

Arthritis, Rheumatoid↗
PubMed1978

The inhibition of polymorphonuclear leukocyte cytotoxicity by dapsone. A possible mechanism in the treatment of dermatitis herpetiformis.

The effect of the sulfone compound 4,4'-diaminodiphenyl sulfone (dapsone) on normal human polymorphonuclear leukocytes (PMNL) has been investigated in vitro. The drug has a dramatically beneficial effect in dermatitis herpetiformis in which the PMNL and immune complexes has been stressed to be of importance for the development of the skin lesions. Pruritus disappears and the inflammatory eruptions clear within a few days of starting therapy. The effect of dapsone has been evaluated on the different stages of phagocytosis. Using dapsone concentrations (1-30 mug/ml) comparable with those found after therapeutic doses, we have found that the drug interferes primarily with the myeloperoxidase (MPO)-H(2)O(2)-halide-mediated cytotoxic system in the PMNL. No effect was observed on random locomotion, chemotaxis, phagocytic ingestion, oxidative metabolism, or the release of lysosomal enzymes. Kinetic studies in a cell-free system with purified MPO revealed a competitive type of inhibition using varying concentrations of NaI. Furthermore, the inhibition resulted in reduced candidicidal activity during phagocytosis of Candida albicans, and reduced cytotoxicity to adjacent mammalian cells measured as the (51)Cr release from virus-induced lymphoma cells. Because the MPO-H(2)O(2)-halide system not only fulfills the antimicrobial activity but is suggested to be a modulator of the inflammatory reaction as well, the action of dapsone in dermatitis herpetiformis may in part be explained by its effect on this system.

Adolescent↗
PubMed1977

Agranulocytosis due to dapsone.

A case of agranulocytosis due to dapsone administered for the treatment of acne vulgaris is described. Agranulocytosis has previously been reported after administration of dapsone for other dermatological disorders, leprosy, and prophylaxis against falciparum malaria. The frequency of agranulocytoses when dapsone was used for malaria prophylaxis in United States servicemen in Vietnam was sufficient to result in its withdrawal from use for this purpose. Caution should therefore be exercised in the administration of dapsone for conditions for which less toxic agents are available.

Adult↗
PubMed1979

Fatal thrombocytopenic hemorrhagic diathesis associated with dapsone administration to a dog.

Dapsone was given for six days to a dog with chronic skin disease. The dog then became weak and anorectic, and it vomited and had purpura caused by severe thrombocytopenic hemorrhagic diathesis. Despite treatment, the dog died a week later. There were clinical and pathologic evidence that the dog's platelets and megakaryocytes had been destroyed during the first few days of dapsone therapy. It was concluded that the syndrome was dapsone-induced and that thrombocytopenia should be considered among the adverse reactions to dapsone in the dog.

Animals↗
PubMed1978

The anti-inflammatory profile of dapsone in animal models of inflammation.

Dapsone has been shown to possess anti-inflammatory activity in a variety of animal models. It possesses oral anti-oedema activity especially pronounced in novel models of acute inflammation, viz. anti-IgG and reversed passive Arthus oedemas. However, it is not very active in the guinea pig u.v. erythema model. It is effective in chronic models such as adjuvant arthritis and the cotton pellet granuloma although multiple administration may also produce cyanosis. Antipyretic and analgesic effects for dapsone have been demonstrated and are similar to those produced by phenylbutazone. It inhibits zymosan-induced beta-glucuronidase release from cultured macrophages and also the activity of this enzyme. Dapsone does not appear to be ulcerogenic in the rat.

Animals↗
PubMed1979

Dapsone and severe hypoalbuminaemia. A report of two cases.

Severe hypoalbuminaemia developed in two patients on long-term dapsone treatment for dermatitis herpetiformis. The patients had been treated with dapsone for 3 and 11 years before the syndrome developed and both recovered completely when dapsone was withdrawn. Albumin-turnover studies revealed a great increase in intravascular albumin catabolism and a modest decrease in synthesis.

Adult↗
PubMed1978

Simultaneous analysis of dapsone and monoacetyldapsone employing high performance liquid chromatography: a rapid method for determination of acetylator phenotype.

1 A rapid, accurate and convenient technique for determination of acetylator phenotype of patients or subjects has not been available for routine clinical application. 2 An improved method for rapid and convenient determination of acetylator phenotype is described. 3 The plasma concentrations of dapsone (DDS) and monoacetyldapsone (MAD) were measured 3 h after a single oral 100 mg dose of dapsone using a specific and sensitive high performance liquid chromatographic assay. 4 The plasma concentration ratio of monoacetyldapsone to dapsone can accurately assess acetylator phenotype in patients or subjects. 5 The clinical applications for this method are discussed.

Acetylation↗
PubMed1976

Bactericidal action of dapsone against Mycobacterium leprae in mice.

Dapsone (4,4'-diaminodiphenylsulfone), incorporated into the mouse chow in a concentration of 0.1 g/100 g of diet, was administered for 1 week to mice in which Mycobacterium leprae had multiplied to the level of 10(6) organisms/footpad. M. leprae were harvested from these and also from control mice, diluted serially, and inoculated into additional mice. The organisms recovered from untreated mice multiplied in passage with a mean doubling time of 12.2 days, and 35% or more of the inoculated organisms were viable, i.e., capable of infecting mice. Growth curves of M. leprae recovered from dapsone-treated animals lagged behind those of organisms from control animals by an average of 78 days, equivalent to 98.8% killing. Foot-by-foot harvests showed that only 0.2% of the M. leprae recovered from treated mice were viable, suggesting that treatment of mice with dapsone had been accompanied by killing of 99.4% of the viable M. leprae.

Animals↗
PubMed1978

Dapsone in the treatment of pemphigus vulgaris.

This is a report on two cases with pemphigus vulgaris effectively controlled by dapsone. In one, dapsone was added to the treatment after a failure of combined prednisone and methotrexate therapy to control the disease completely. It is suggested that dapsone may offer a means in an attempt to minimize adverse reactions met with during the long corticosteroid regimen required in pemphigus.

Adult↗
PubMed1976

Dapsone chemotherapy of Mycobacterium leprae infection of the neonatally thymectomized Lewis rat.

In order to learn whether the neonatally thymectomized Lewis rat (NTLR) infected with Mycobacterium leprae could serve as a model for chemotherapeutic studies in a situation resembling that found in human lepromatous leprosy, NTLR inoculated with M. leprae either locally or intravenously 9 to 16 months earlier were treated for from 1.5 to 8.5 months with dapsone (4,4'-diaminodiphenylsulfone, DDS) incorporated in the rat chow in the concentration providing the minimal inhibitory concentration of the drug for M. leprae and in the 100-fold larger concentration. NTLR were killed at intervals; the M. leprae were counted and passed to mice. Treatment with the smaller dosage of dapsone neither killed M. leprae nor reduced the number of organisms in the bacterial populations, whereas treatment with the larger dosage both killed M. leprae and reduced their numbers. The rate at which the organisms were killed (i.e., rendered noninfective for mice) was much the same as that in patients treated with dapsone in comparable dosage. The dead organisms were removed from the rat tissues at a faster rate than encountered in patients. The NTLR may indeed be suitable for chemotherapeutic studies relevant to man. In addition, the more rapid disappearance of dead M. leprae from the rat tissues may facilitate the study of treatment regimens designed to eradicate persisting viable organisms.

Animals↗
PubMed2026

A cost-effective conventional endpoint PCR assay for HLA-B*13:01 genotyping to guide personalized dapsone therapy in leprosy in low-resource settings.

BACKGROUND: Dapsone is a drug used to treat leprosy. Dapsone causes a highly morbid and potentially fatal severe drug hypersensitivity reaction (DHS) in 1-3% of leprosy cases. The allele HLA-B*13:01 is a known genetic risk factor for DHS. However, resource-intensive genotyping methods preclude its testing in resource-limited settings. This study aimed to develop an endpoint PCR assay to detect the presence of HLA-B*13:01. RESEARCH DESIGN AND METHODS: DNA was extracted from blood samples of leprosy patients at Anandaban Hospital, Nepal (2022-24). A duplex endpoint PCR was optimized and validated against a previously validated commercial qPCR method and NGS (next‑generation sequencing). RESULTS: In 113 samples, duplex PCR showed 100% (95% CI: 79.4-100%) sensitivity and 100% specificity (95% CI: 96.2-100%) compared to the validated qPCR method. The same accuracy was confirmed in 58 NGS-typed samples (concordance 98.3%, 95% CI: 90.7-99.9%). The assay reliably differentiated HLA-B*13:01 from closely related allele. Analytical sensitivity reached a lower detection limit of 100 genome equivalents (0.67 ng DNA/reaction). CONCLUSION: The developed duplex endpoint PCR offers a simple and affordable method for detecting HLA-B*13:01, suitable in low-resource settings. Its use may significantly reduce the risk of DHS by guiding safer drug choices prior to MDT initiation.

Humans↗