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PubMed1993

Reduction of dapsone hydroxylamine to dapsone during methaemoglobin formation in human erythrocytes in vitro--II. Movement of dapsone across a semipermeable membrane into erythrocytes and plasma.

We have used an in vitro two-compartment model, to investigate the ability of dapsone, formed by erythrocyte-mediated detoxification of its hydroxylamine metabolite, to escape the cells and cross a semi-permeable membrane into both plasma and other erythrocytes. Both diethyl dithiocarbamate (DDC) treated and untreated erythrocytes were incubated with dapsone hydroxylamine and dialysed against either fresh cells or plasma. Methaemoglobin was predominantly detectable in compartment A although the presence of low levels of methaemoglobin in compartment B indicated that the hydroxylamine itself had crossed the membrane. In contrast to methaemoglobin disposition, recovery of dapsone was higher (P < 0.05) in compartment B compared with A for all three treatment groups at 30 and 60 min, but not at the remaining time points. Regression analysis of the cumulative recovery of dapsone over 150 min in all three treatment groups for both compartments A and B showed correlation coefficients close to unity. In compartment A, analysis of the mean slopes of the regression lines indicated that, overall, significantly more dapsone was recovered from group 1 (erythrocytes, hydroxylamine and DDC dialysed against untreated red cells) compared with group 3 (erythrocytes and hydroxylamine dialysed against plasma) (0.22 +/- 0.05 vs 0.09 +/- 0.005; P < 0.025). Also in compartment A, significantly more dapsone was recovered from group 2 (erythrocytes and hydroxylamine dialysed against untreated red cells) compared with group 3 (erythrocytes and hydroxylamine dialysed against plasma: 0.16 +/- 0.02 vs 0.09 +/- 0.005). In compartment B, dapsone recovery was significantly greater in group 1 (erythrocytes, hydroxylamine and DDC dialysed against untreated red cells; slope of regression line: 0.59 +/- 0.05) compared with group 2 (erythrocytes and hydroxylamine dialysed against untreated red cells; slope of line: 0.28 +/- 0.02, P < 0.005). In addition, dapsone recovery was significantly greater in group 1 (0.59 +/- 0.05) compared with group 3 (erythrocytes and hydroxylamine dialysed against plasma; 0.21 +/- 0.02, P < 0.005). Dialysis of erythrocytes with dapsone itself over 120 min caused no detectable methaemoglobin formation. The process of erythrocyte-mediated dapsone formation from its hydroxylamine may feasibly occur in vivo and contribute to the systemic persistence and therapeutic effect of dapsone.

Cell Membrane Permeability↗
PubMed1994

Pharmacokinetics and safety of weekly dapsone and dapsone plus pyrimethamine for prevention of pneumocystis pneumonia.

The safety and pharmacokinetics of weekly dapsone and weekly dapsone plus pyrimethamine were examined in adult patients with human immunodeficiency virus infection who were at risk for pneumocystis pneumonia because of a prior episode or a CD4+ T-cell count less than 250 cells per mm3. Groups of patients received 100, 200, and 300 mg of dapsone as a single weekly dose. The maximum tolerated dose of weekly dapsone was established as 200 mg per week in patients receiving at least 500 mg of zidovudine concomitantly. This dose of dapsone was then found to be well tolerated when combined with pyrimethamine at 25 mg. Further patients were randomized to dapsone at 200 mg or dapsone at 200 mg plus pyrimethamine at 25 mg once weekly. Twenty-six patients each were followed for a median of 33 weeks on dapsone alone and 45 weeks on the combination. Seven patients in each group withdrew because of toxicity. Five patients receiving dapsone developed documented pneumocystis pneumonia, while four and two patients receiving dapsone plus pyrimethamine developed documented and presumptive pneumocystis pneumonia, respectively. To evaluate the tolerability of a higher dose of pyrimethamine, 11 patients had their regimen changed to dapsone at 200 mg plus pyrimethamine at 75 mg, which was well tolerated by 10 of the patients for a median period of 11 weeks. The pharmacokinetics of dapsone and pyrimethamine were examined by using a population pharmacokinetic model. Decreases in the apparent volume of the peripheral compartment were observed when multiple-dose regimens of dapsone were compared with single-dose dapsone and when multiple-dose regimens of dapsone with pyrimethamine were compared with multiple-dose dapsone alone. When administered weekly, dapsone at 200 mg and dapsone at 200 mg with pyrimethamine at 25 mg are both well-tolerated regimens. This preliminary study suggests that the efficacy of these regimens in preventing pneumocystis pneumonia, however, may be less than that of trimethoprim-sulfamethoxazole.

AIDS-Related Opportunistic Infections↗
PubMed1993

Reduction of dapsone hydroxylamine to dapsone during methaemoglobin formation in human erythrocytes in vitro.

The fate of the toxic metabolite of dapsone, dapsone hydroxylamine, has been studied in the human red cell. Twice-washed red cells were incubated at 37 degrees with dapsone hydroxylamine: at 3 and 5 min, 27.0 +/- 2.2 and 33.2 +/- 2.7% of the haemoglobin had been converted to methaemoglobin, leading to a maximum at 45 min (45 +/- 1.8%). HPLC analysis revealed that parent amine was produced from dapsone hydroxylamine during methaemoglobin formation in the red cells. At 3 min, conversion of dapsone hydroxylamine to dapsone reached 7.0 +/- 3.9% leading to a maximum at 30 min (18.1 +/- 3.7%). There was a linear relationship between hydroxylamine-dependent methaemoglobin formation and conversion of hydroxylamine to dapsone (r = 0.97). At 4 degrees, methaemoglobin and dapsone formation was greatly retarded, and did not exceed 10%. Co-incubation of diethyl dithiocarbamate (DDC) with dapsone hydroxylamine and red cells led to a marked increase in methaemoglobin formation (61.4 +/- 3.4%) compared with hydroxylamine and red cells alone (45.0 +/- 1.8%, P < 0.001) at 45 min, and conversion of dapsone hydroxylamine to dapsone was almost doubled at 45 min (35.7 +/- 5.3%) compared with hydroxylamine and red cells (18.1 +/- 2.5%). A linear relationship between methaemoglobin formation and dapsone formation (r = 0.96) was also shown to occur in the presence of DDC. Incubation of red cells with DDC and dapsone hydroxylamine caused a significantly greater reduction in glutathione levels (98.3 +/- 1.6%) compared with red cells and dapsone hydroxylamine alone (84.8 +/- 2.7%) at 5 min (P < 0.001), although there was no significant difference between the groups at 15 min (96.9 +/- 2.6 vs 98.1 +/- 2.2%). Intra-erythrocytic glutathione was then depleted by 75 +/- 3.4%, by pretreatment with diethyl maleate (6 mM), and these cells in the presence of the hydroxylamine showed a significant fall in both methaemoglobin generation (29.7 +/- 1.2 vs 35.0 +/- 1.7%) and parent amine formation (11.1 +/- 0.2 vs 16.5 +/- 1.1%) compared with untreated red cells at 45 min. It is possible that a cycle exists between hepatic oxidation of dapsone to its hydroxylamine and reduction to the amine within the red cell, which may lead to re-oxidation by hepatic cytochrome P450. This process may contribute to the persistence of the drug in vivo.

Dapsone↗
PubMed1999

Development of dapsone toxicity in patients with inflammatory dermatoses: activity of acetylation and hydroxylation of dapsone as risk factors.

BACKGROUND: Alternative independent routes of dapsone metabolism include N-hydroxylation to the hydroxylamine, a potentially toxic metabolite, by cytochrome P450 enzymes and acetylation to a nontoxic metabolite by N-acetyltransferase. Potentially, therefore, the relative extents of these two routes in an individual could determine the occurrence of adverse reaction with dapsone therapy. METHODS: Phenotypic activity of these two routes of metabolism was assessed in 18 patients receiving longterm dapsone therapy for inflammatory dermatoses and was related to the development of dapsone toxicity. N-Hydroxylation was assessed by the dapsone recovery ratio, a ratio of dapsone hydroxylamine to the sum of hydroxylamine and dapsone in 8-hour urine, whereas N-acetylation was assessed by the acetylation ratio, a ratio of monoacetyldapsone to dapsone in 8-hour plasma sample after an oral dose of dapsone. RESULTS: There was wide intersubject variation in both the acetylation ratio and the dapsone recovery ratio, but both phenotypic measures remained stable within individuals. The dapsone recovery ratio showed a tendency toward being lower in fast than in slow acetylators, but this was not statistically significant. There was an inverse relationship between acetylation and hydroxylation (r = -0.69; P < .005) at steady state that was not apparent after the first dose. Neurotoxicity developed in two subjects and hemolytic anemia developed in two subjects. Plasma levels of dapsone in these four subjects were similar to those in subjects who showed no toxicity. All four were slow acetylators and three were rapid hydroxylators, consistent with the toxic nature of dapsone hydroxylamine. CONCLUSIONS: These observations are consistent with what is known about the toxicity profile of dapsone metabolites and suggest that assessing N-acetylation and N-hydroxylation capacities can help to identify subjects at increased risk of a toxic response. This approach of assessing the phenotypic measures of drug-metabolizing activity to predict adverse reaction may also apply to other drugs with metabolic-based adverse effects.

Acetylation↗
PubMed1991

Inhibition of dapsone-induced methaemoglobinaemia by cimetidine in the rat during chronic dapsone administration.

Dapsone undergoes N-acetylation to monoacetyl dapsone as well as N-hydroxylation to a hydroxylamine which is responsible for the haemotoxicity (i.e. methaemoglobinaemia; Met Hb) of the drug. Since dapsone is always given chronically, we have investigated the ability of cimetidine to inhibit Met Hb formation caused by repeated dapsone administration. The drug was given (i.p.) to four groups (n = 6 per group) of male Wistar rats, 300-360 g. Group I received 10 mg kg-1 at 1, 24, 48 and 72 h. Group II received 10 mg kg-1 at 1, 8, 24, 32, 48, 56, 72 and 80 h. Groups III and IV received the drug as for groups I and II, respectively, as well as cimetidine (50 mg kg-1) 1 h before each dose of dapsone. Twice daily dapsone administration (Group II) resulted in a significantly greater (P less than 0.05) Met Hb AUC (757 +/- 135 vs 584 +/- 115% Met Hb h), dapsone AUC (140 +/- 17.5 vs 113 +/- 13.0 micrograms h mL-1) and monoacetyl dapsone AUC (48.2 +/- 18.3 vs 10.8 +/- 4.6 micrograms h mL-1) compared with a single daily dapsone dose (group I). The administration of cimetidine before the once daily dose of dapsone (group III) resulted in a significant (P less than 0.05) fall in Met Hb (302 +/- 179 vs 584 +/- 115% Met Hb h) and an increase in both the dapsone (151 +/- 22.2 vs 113 +/- 13.0 micrograms h mL-1) and monoacetyl dapsone AUC values (33.6 +/- 5.8 vs 10.8 +/- 4.0 micrograms h mL-1) compared with a single daily dose of dapsone (group I).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Inhibition of neutrophil adherence to antibody by dapsone: a possible therapeutic mechanism of dapsone in the treatment of IgA dermatoses.

Dapsone is frequently effective in cutaneous diseases characterized by antibody deposition and accumulation of neutrophils. We hypothesized that this mechanism of action of dapsone may involve the inhibition of neutrophil adherence to antibody. The neutrophil adherence assay, which measures the binding of neutrophils to basement membrane zone-bound antibody on skin sections, was used to evaluate the effect of dapsone on neutrophil adherence to immunoglobulin A and immunoglobulin G. We evaluated the effect of dapsone on adherence of normal neutrophils to immunoglobulin A and immunoglobulin G from sera of linear immunoglobulin A bullous dermatosis and bullous pemphigoid patients, respectively. Linear immunoglobulin A bullous dermatosis or bullous pemphigoid antibody were bound to the basement membrane zone of normal skin sections as a substrate for the neutrophil adherence assay. Dapsone was added directly to the neutrophils or to the antibody source in concentrations of 0-50 micrograms/ml (pharmacologic range). Addition of dapsone to neutrophils produced an incremental inhibition of neutrophil adherence up to 75% at 50 micrograms/ml. Dapsone produced similar inhibition when added directly to the antibody itself, despite washing prior to usage in the neutrophil-adherence assay. Control specimens including irrelevant fractions of patient sera failed to demonstrate binding. Serum from a patient on dapsone therapy also showed inhibition of neutrophil adherence compared to the same patient on no therapy. We conclude that dapsone inhibits the adherence of neutrophils to basement membrane zone antibody in a dose-dependent manner. This may be related to an effect directly on antibody. This inhibition may contribute to the clinical efficacy of dapsone in antibody-mediated diseases.

Adult↗
PubMed2003

Dapsone induced cholangitis as a part of dapsone syndrome: a case report.

BACKGROUND: Dapsone can rarely cause a hypersensitivity reaction called dapsone syndrome, consisting of fever, hepatitis, exfoliative dermatitis, lymphadenopathy and hemolytic anemia. Dapsone syndrome is a manifestation of the DRESS (drug rash with eosinophilia and systemic symptoms) syndrome which is a serious condition that has been reported in association with various drugs. Cholangitis in dapsone syndrome has not been reported so far in the world literature. CASE PRESENTATION: We report a patient who presented with fever, exfoliative dermatitis, jaundice and anemia within three weeks of starting of dapsone therapy. These features are typical of dapsone syndrome, which is due to dapsone hypersensitivity and is potentially fatal. Unlike previous reports of hepatitic or cholestatic injury in dapsone syndrome we report here a case that had cholangitic liver injury. It responded to corticosteroids. CONCLUSION: We conclude that cholangitis, though unusual, can also form a part of dapsone syndrome. Physicians should be aware of this unusual picture of potentially fatal dapsone syndrome.

Adult↗
PubMed1988

Role of dapsone hydroxylamine in dapsone-induced hemolytic anemia.

The hemolytic anemia which frequently accompanies treatment of individuals with dapsone and other arylamine drugs is believed to be caused not by the parent drugs per se, but rather by metabolites which are formed during the clearance of the drugs in vivo. To determine whether the N-hydroxyarylamine metabolites of dapsone could be responsible for dapsone-induced hemolysis, dapsone, dapsone hydroxylamine (DDS-NOH) and monoacetyldapsone hydroxylamine were administered to rats which had previously received 51Cr-labeled red blood cells. All three compounds caused an increase in the rate of disappearance of radioactivity from the blood as compared with saline-treated controls. In parallel in vitro studies, incubation of 51Cr-labeled red blood cells with DDS-NOH, but not dapsone or monoacetyldapsone, induced a decrease in survival time of the radiolabeled cells when they were reintroduced into isologous rats. The disappearance of radioactivity from the blood was matched by its selective uptake into the spleen. The amount of damage (as measured by decreased red cell survival in vivo) was proportional to both concentration and time of exposure to DDS-NOH. The area under the blood concentration vs. time curve for total arylhydroxylamines (DDS-NOH + monacetyldapsone hydroxylamine) in rats given a hemotoxic dose of dapsone was similar to that of rats given an equitoxic dose of DDS-NOH. Collectively, these data indicate that the hydroxylamine metabolites of dapsone are direct acting hemolytic agents that are formed from dapsone in sufficient amounts to account for their being the sole mediators of dapsone-induced hemolytic anemia in the rat.

Anemia, Hemolytic↗
PubMed1994

Reduction of dapsone hydroxylamine to dapsone during methaemoglobin formation in human erythrocytes in vitro. III: Effect of diabetes.

The fate of dapsone hydroxylamine has been investigated in diabetic and normal human erythrocytes. In erythrocytes from four type 1 (insulin dependent) diabetic subjects, there was a significant decrease in dapsone hydroxylamine-mediated methaemoglobin formation compared with cells drawn from normal individuals (P < 0.01). However, the ability of the diabetic cells to detoxify the hydroxylamine to dapsone was not correspondingly reduced and was not different to normal cells. The initial rate of the accelerating effect of diethyl dithiocarbamate (DDC) on hydroxylamine-mediated methaemoglobin and dapsone formation was significantly reduced in diabetic compared with normal cells. There was no significant difference in hydroxylamine-dependent methaemoglobin formation between diabetic erythrocytes pretreated with either statil or sorbinil and untreated diabetic cells. Dapsone recovery in diabetic erythrocytes incubated with statil was not significantly different from statil-free incubations. However, in the presence of sorbinil, there was a marked reduction in dapsone formation at all four time points, (P < 0.001 at 15 min). Mean measured levels of glutathione did not differ significantly between the normal (380 +/- 30.9 mg/L; N = 8) and diabetic (349 +/- 58.7 mg/L; N = 8) volunteers. In summary, although diabetic erythrocytes were less sensitive to the effect of dapsone hydroxylamine-mediated methaemoglobin formation in comparison with normal cells, glutathione-dependent hydroxylamine reduction to dapsone was unaffected.

Dapsone↗
PubMed1995

Cimetidine improves the therapeutic/toxic ratio of dapsone in patients on chronic dapsone therapy.

We have previously shown that cimetidine, given concurrently for 2 weeks to patients on chronic dapsone therapy, reduced methaemoglobinaemia by inhibiting the formation of the toxic hydroxylamine metabolite of dapsone. The aim of the present study was to examine the effect of this combination on the benefit/toxic ratio of dapsone over a longer period. Eight patients (six dermatitis herpetiformis, one linear IgA disease, one folliculitis decalvans) on long-term dapsone 50-100 mg daily, took cimetidine 1.6 g daily concurrently for 3 months. At 3-weekly intervals, a clinical assessment was made, plasma dapsone and methaemoglobin were measured, and parameters of oxidative haemolysis were monitored. The dapsone level rose from 2298 +/- 849 ng/ml (mean +/- SD) at baseline to 3006 +/- 1131 ng/ml at week 3 of cimetidine (P < 0.01). This rise in plasma dapsone was sustained during cimetidine administration, falling to 2446 +/- 954 ng/ml when cimetidine was stopped (P < 0.02). The methaemoglobin fell from 5.5 +/- 2.2% (mean +/- SD) at baseline to 3.9 +/- 1.1% at week 3 (P < 0.01), and remained low until week 12, when there was a return to baseline values (P < 0.01). The haemoglobin did not change from the baseline of 12.7 +/- 0.3 g/dl (mean +/- SD), and other parameters of haemolysis were unaltered. There was a fall in the visual analogue score for headache (P < 0.05), but this was not associated with any deterioration in control of the skin disorders. Hence, long-term concurrent cimetidine results in increased plasma dapsone levels without increased haemolysis, and is accompanied by reduced methaemoglobinaemia for more than 2 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Reduction of dapsone hydroxylamine to dapsone during methaemoglobin formation in human erythrocytes in vitro. IV: Implications for the development of agranulocytosis.

We have studied the efflux of dapsone hydroxylamine from normal and diabetic erythrocytes by the use of a two-compartment (1 and 2) in vitro dialysis system, in order to model the in vivo blood supply to the bone marrow. When both types of erythrocytes were dialysed against mononuclear leucocytes, the hydroxylamine crossed the membrane and caused significantly greater white cell death compared with dialysis of leucocytes against untreated erythrocytes. However, in the case of both normal and diabetic cells, the presence of the glutathione depletor diethyl maleate (DEM) caused a marked reduction in movement of hydroxylamine from compartment 1 to 2. Diethyl dithiocarbamate (DDC), a methaemoglobin accelerant, caused a marked reduction in movement of hydroxylamine from erythrocytes (diabetic and normal) in compartment 1 to 2 which led to a significant reduction in white cell death compared with the absence of DDC (18.3 +/- 5.5 vs 34.8 +/- 8.1%, P < 0.05). Dapsone recovery from compartment 1 rose significantly in the presence of DDC compared with control in both erythrocyte types. In contrast, recovery of dapsone from normal erythrocytes incubated in compartment 1 was significantly reduced by the presence of DEM compared with control, although there was no difference between control and DEM-treated diabetic cells. Dapsone analysis in compartment 2 revealed a significant increase in dapsone recovery in both diabetic (11.3 +/- 1.1%) and normal (11.9 +/- 1.1%) erythrocytes in the presence of DDC compared with diabetic (3.3 +/- 0.4%) and normal control (4.8 +/- 2.0%, P < 0.001). The presence of DEM in compartment 1 caused a significant fall in dapsone recovery in compartment 2 (3.7 +/- 0.26) compared with control (4.7 +/- 0.36%, P < 0.05). Hence, dapsone hydroxylamine is capable of leeching out of normal and diabetic erythrocytes, traversing a semipermeable membrane and causing toxicity to human mononucleocyte cells in vitro. This process may be one of the first stages in immune-mediated agranulocytosis.

Agranulocytosis↗
PubMed2000

Bioequivalence of a propylene glycol-based liquid dapsone preparation and dapsone tablets.

The bioequivalence of a proprietary liquid dapsone preparation and commercially available dapsone tablets was studied. Twelve adult volunteers received dapsone doses with 8 oz of water one to two hours after their usual breakfast. Each subject received an initial 100-mg dose of a propylene glycol-based liquid preparation of dapsone and, two weeks later, a 100-mg dapsone tablet (both from Jacobus Pharmaceutical Company, Princeton, NJ). Blood samples were collected before and at intervals up to 96 hours after the administration of each dose. Serum dapsone concentrations were determined by high-performance liquid chromatography, and pharmacokinetic values were calculated by model-independent analysis. The area under the concentration-versus-time curve and the maximum serum concentration for the two formulations met the criteria for bioequivalence. Time to maximum serum concentration tended to be lower for the liquid, but not significantly. The liquid and tablet formulations of dapsone studied were found to be bioequivalent and may be used interchangeably.

Adult↗
PubMed1994

Relapse rates in patients treated with dapsone monotherapy and combinations of dapsone and thiambutosine, thiacetazone, isoniazid and streptomycin in the pre-MDT era.

Relapse rates were studied in patients from northern Thailand who were started on dapsone monotherapy between 1949 and 1976. Included are a group of patients who, for various reasons, also received combinations of dapsone and thiambutosine, thiacetazone, isoniazid and streptomycin. The overall relapse rate in paucibacillary patients on dapsone monotherapy only was 2.7 per 1000 person-years at risk (PYR) (average observation period 13.9 years). In the multibacillary patients who received dapsone monotherapy only, the relapse rate was 10.5 per 1000 PYR (average observation period 12.4 years). In both groups it was found that 50% of the relapses occurred after the seventh year of follow up. The overall relapse rate in those patients whose treatment included thiambutosine, thiacetazone, isoniazid and/or streptomycin for at least 3 months was 17.9 per 1000 PYR (average observation period 11.9 years). The difference with the multibacillary patients treated with dapsone monotherapy only is not significant. It is concluded that alternative antileprosy drugs included in therapy regimens with dapsone in the pre-MDT era did not result in relapses occurring less often.

Dapsone↗
PubMed1995

Dapsone-induced hemolytic anemia: effect of dapsone hydroxylamine on sulfhydryl status, membrane skeletal proteins and morphology of human and rat erythrocytes.

Dapsone hydroxylamine is a direct-acting hemolytic agent responsible for dapsone-induced hemolytic anemia in the rat. In the present study, we compared the responsiveness of rat and human red cells to dapsone hydroxylamine-induced cellular changes. Dapsone hydroxylamine induced a rapid and concentration-dependent loss of erythrocytic reduced glutathione content with a concomitant increase in protein-glutathione mixed disulfide formation in both human and rat red cell suspensions. However, the rate of mixed disulfide formation in human cells was considerably slower than that in rat cells and was preceded by a transient increase in oxidized glutathione (glutathione disulfide) formation. Sodium dodecylsulfate-polyacrylamide gel electrophoresis and immunoblotting analysis of membrane ghosts from human red cells revealed changes in skeletal proteins that in general were similar to those observed with rat cells, including a loss of protein band 2.1 and the appearance of membrane-bound hemoglobin. Notable differences were the resistance to loss of band 4.2 and a considerably higher amount of protein aggregation in human ghosts. Although the morphology of human red cells was altered, the incidence and degree of change were considerably less than those of rat red cells. Furthermore, the concentration of dapsone hydroxylamine required to induce damage in human red cells (175-750 microM) was significantly higher than that required for rat red cells (50-175 microM), suggesting that human cells are probably less sensitive than rat cells to dapsone hydroxylamine-induced oxidative damage.

Anemia, Hemolytic↗
PubMed1983

Acute dapsone intoxication: clinical findings and effect of oral charcoal and haemodialysis on dapsone elimination.

Three patients were treated after ingestion of an overdose of dapsone (1-10 g). A considerable acute cyanosis due to methaemoglobinaemia was followed by a late haemolysis within 1-2 weeks. Activated charcoal given orally in multiple doses (20 g X 4/day) shortened the half-life of dapsone to 12.7 +/- 0.7 hours, i.e. to about 1/3-1/6 of the preceding control value. The half-life of dapsone was about 10 hours during each of the three 5-hour haemodialysis treatments given to one patient. However, owing to the rebound phenomenon between haemodialyses, the half-life of dapsone from the start of the first to the end of the third haemodialysis was 26 hours. The efficacy of orally administered activated charcoal is fully comparable to that of haemodialysis in increasing the rate of elimination of dapsone and its metabolite monoacetyldapsone. Activated charcoal is cheap, it can be administered anywhere and its administration rarely involves complications.

Administration, Oral↗
PubMed1986

Spot test for detection of dapsone in urine: an assessment of its validity and interpretation in monitoring dapsone self-administration.

This study aimed to assess the validity and interpretation of the spot test for monitoring dapsone self-administration that employs filter paper impregnated with a modified Ehrlich's reagent. Urine specimens obtained from 20 volunteers, who took 100 mg dapsone for four days in succession, were investigated by this test. Findings indicate that spot tests will be negative after an average of three missed doses of dapsone, if compared with a standard of 5 micrograms dapsone per ml of urine. No negative spots are expected in fully compliant patients, and no positive spots are expected in patients who did not take dapsone for a week or longer. In the context of the treatment goal, it is argued that this degree of sensitivity makes the spot test a valid tool for the monitoring and management of patient compliance in leprosy control programs.

Dapsone↗
PubMedDate not supplied

Comparative value of Dapsone "spot test" and Dapsone "tile test" in leprosy control programme.

The sensitivity of Dapsone "spot test" with modified Ehrlich's reagent (Balakrishnan, 1968) and Dapsone "tile test" using Barton-Marshall reagents (Irudayraj, 1981)--both being qualitative tests for screening of dapsone in urine are compared with Dapsone/creatinine ratio--a quantitative test (Ellard, 1974). 316 urine samples were processed by paramedical worker in the fields for Dapsone "Tile test" and Dapsone "Spot test". The same samples were brought to the laboratory and subjected to these two tests besides Dapsone/creatinine estimation. These three tests correlated well at the level of 91%. The results obtained by paramedical workers and experienced worker at the laboratory are also showed 97% concordance. An earlier investigations revealed that monitoring through frequent and surprise check-up of urines for drug content (4-5 samples/year/patient) and subsequent motivation and persuation of leprosy patient, the irregularity rate of drug consumption by patient could be brought down from 36% to 17% in one year. The kit for performing DDS "spot test" and DDS "tile test" being light and easy to carry in the field and the tests being simple to perform with reliable results. This procedure is recommended to be applied in the field on a mass scale. The routine frequent and surprise checking of urine for drug content will give early idea about irregularity status of drug consumption by patients as compared to the judgement relying on clinical assessment and reduction of bacteriological index of infectious patients.

Colorimetry↗
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↗