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PubMed2004

Dapsone-induced hypersensitivity pneumonitis mimicking Pneumocystis carinii pneumonia in a patient with AIDS.

Interstitial pneumonitis, often related to infectious etiologies, occurs commonly in HIV-infected patients. However, hypersensitivity pneumonitis from noninfectious etiologies, including environmental stimuli or drug exposure, is an unusual etiology of interstitial pneumonitis in HIV-infected patients. We report a patient with AIDS who developed a dapsone-induced hypersensitivity pneumonitis mimicking Pneumocystis carinii (PCP) pneumonia. We believe drug-induced hypersensitivity pneumonitis should be considered in the differential diagnosis of interstitial pneumonia in HIV-infected patients in whom infectious etiologies have been ruled out.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Thrice-weekly cotrimoxazole is better than weekly dapsone-pyrimethamine for the primary prevention of Pneumocystis carinii pneumonia in HIV-infected patients.

OBJECTIVE: To compare the efficacy and safety of two intermittent regimens for the simultaneous primary prevention of Pneumocystis carinii pneumonia (PCP) and toxoplasmosis in HIV-infected patients. DESIGN: Prospective randomized open trial. SETTING: HIV outpatient clinic of an Infectious Disease Service and a 1000-bed university teaching hospital. PATIENTS: A total of 166 HIV-infected patients with a CD4 cell count < 200 x 10(6)/l or a CD4 percentage < 20%, without previous PCP or toxoplasmosis. INTERVENTION: Patients were randomized to oral (1) cotrimoxazole [160 mg trimethoprim (TMP) and 800 mg sulphamethoxazole (SMX)] twice a day on Mondays, Wednesdays and Fridays (n = 81), or (2) dapsone (100 mg) plus pyrimethamine (25 mg) (DP) once a week (n = 85). MAIN OUTCOME MEASURES: Clinical and biological evaluation was performed every 30-60 days. End-points were PCP, toxoplasmosis and death. Adverse reactions were considered as defined in the protocol. RESULTS: After a mean follow-up of 380 days, intention-to-treat analysis revealed that DP patients had a higher rate of PCP [13 out of 85 (15.2%) versus three out of 81 (3.7%); P = 0.01]. The cumulative rates of PCP at 12 and 24 months were 5 and 42% for DP patients and 3 and 10% for TMP-SMX patients, respectively (Mantel-Cox, P = 0.0007). Of the 29 patients who died during follow-up, 14 were in the TMP-SMX group and 15 in the DP group (not significant). Two patients in the TMP-SMX group and three in the DP group developed toxoplasmosis (not significant). Adverse reactions were common (66.7% of TMP-SMX patients and 42.4% of DP patients; P = 0.001). However, only 12.3% of TMP-SMX patients and 2.3% of DP patients (P = 0.01) had to discontinue therapy because of toxicity. CONCLUSIONS: At the given doses, DP was inferior to TMP-SMX in preventing first episodes of PCP. Although more patients and a longer follow-up are required, the regimens appeared to prevent toxoplasmosis equally well.

AIDS-Related Opportunistic Infections↗
PubMed1985

Simultaneous estimation of serum concentrations of dapsone, monoacetyldapsone, and pyrimethamine in Chinese men on maloprim for malaria prophylaxis using reversed-phase high performance liquid chromatography.

A reversed-phase high performance liquid chromatography method was developed to simultaneously estimate serum concentrations of dapsone (DDS), monoacetyldapsone (MADDS), and pyrimethamine (PYR) in 34 young adult Chinese men after they had taken the sixth weekly dose of Maloprim for malaria prophylaxis. Serum concentrations of DDS, MADDS, and PYR after 24 h were (mean +/- SEM) 374 +/- 31.3, 310 +/- 30.4, and 121 +/- 7.9 ng/ml, respectively. The 72-h serum concentrations of DDS, MADDS, and PYR were (mean +/- SEM) 134 +/- 21.6, 115 +/- 17.9, and 80 +/- 7.2 ng/ml, respectively. Serum concentrations of DDS and MADDS in many subjects after 120 h were less than 20 ng/ml, while mean +/- SEM concentration of PYR was 53 +/- 5.6 ng/ml. Acetylator phenotyping of the subjects showed that there were 31 (91%) fast acetylators, three (9%) intermediate acetylators, and no slow acetylators.

Acetylation↗
PubMed1995

High-performance liquid chromatography determination of dapsone, monoacetyldapsone, and pyrimethamine in filter paper blood spots.

A high-performance liquid chromatography method for the simultaneous analysis of dapsone (DDS), the major metabolite of DDS, monoacetyldapsone (MADDS), and pyrimethamine (PYR) was modified for capillary blood samples obtained by finger prick and dried on filter paper. Limit of quantitation using 150 microliters whole blood dried on filter paper was found to be 20 ng/ml for DDS and PYR and 15 ng/ml for MADDS (precision < 15%). The clinically relevant concentrations of DDS are 50-2,000 ng/ml and for PYR 25-150 ng/ml. No interference from several drugs were observed. The accuracy of the filter paper method and the original whole-blood method was almost comparable. Standardization could therefore be obtained by the more simple whole-blood method. Dried filter paper samples stored at 19-22 degrees C were stable for months and for 2 weeks stored at 35 degrees C. The concentrations of simultaneously collected capillary blood and conventional venous blood samples correlated well. The present method using capillary blood dried on filter paper is reliable, simple, sensitive, and applicable in the field with limited technical facilities.

Anti-Infective Agents↗
PubMed1997

Anti-oxidative therapy with oral dapsone improved HCV antibody positive annular elastolytic giant cell granuloma.

A 72-year-old fisherman who was positive for the HCV antibody developed an annular, erythematous, infiltrated lesions on sun-exposed areas. The lesions were diagnosed as annular elastolytic giant cell granuloma both clinically and histologically. Topical corticosteroid and cryotherapy with liquid nitrogen for several months failed to improve the lesions. We then started dapsone, a known anti-oxidant, at 50 mg/day. A month later, the margins of the erythematous lesions faded, and the infiltration gradually decreased. No recurrence has been observed for one year after the start of the therapy. Anti-oxidative therapy appears to be effective for annular elastolytic giant cell granuloma and could be an alternate therapy for refractory granulomatous disease.

Administration, Oral↗
PubMed2001

A case of childhood generalized pustular psoriasis treated with dapsone.

Acute generalized pustular psoriasis (GPP) is a rare, sometimes fatal, exudative form of psoriasis characterized by acute febrile pustular psoriasis. Unlike the adult forms, GPP in childhood tends to undergo a more benign course. It may resolve spontaneously with only supportive treatment, but may sometimes be life threatening and resistant to therapy. We report a case of GPP in 7-year-old girl treated successfully with dapsone.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2004

Behçet's syndrome with pyoderma-gangrenosum-like lesions treated successfully with dapsone monotherapy.

Behçet's syndrome (BS) is a rare multisystem disorder belonging to a group of neutrophilic dermatoses. We report a 65-year-old male patient who had suffered from recurrent painful orogenital ulcers for 50 years from the age of 15 and started developing pustular and bullous lesions evolving into non-healing ulcers similar to those seen in pyoderma gangrenosum (PG) two months prior to presenting to us. There was no evidence of systemic disease or malignancy. Routine baseline investigations were within normal limits. The patient was treated successfully with dapsone, antibiotics, and local wound care.

Administration, Oral↗
PubMed2005

Adult Henoch-Schönlein purpura with severe abdominal pain treated with dapsone and factor XIII concentrate.

We describe an adult patient with Henoch-Schönlein purpura who had arthralgia, severe abdominal pain, and low plasma factor XIII activity. Corticosteroids were not used because of his history of multidrug-resistant pulmonary tuberculosis. Dapsone had no immediate effect on his abdominal pain, but appeared to have some effect on the purpura and arthralgia. Marked improvement of the abdominal pain was observed immediately after the administration of factor XIII concentrate. Factor XIII concentrate may be useful for alleviating abdominal pain in Henoch-Schönlein purpura patients when corticosteroids are contraindicated

Abdominal Pain↗
PubMed1980

Pharmacokinetics and protein binding interactions of dapsone and pyrimethamine.

1 Seven normal volunteers received oral doses of 100 mg dapsone (DDS), 25 mg pyrimethamine (PYR) singly or in combination in random order. 2 Plasma and salivary DDS and plasma monoacetyldapone (MADDS) and PYR were estimated simultaneously by a hitherto unpublished quantitative absorption thin layer chromatographic method. This assay was shown to be satisfactory for pharmacokinetic studies. 3 The half-life of DDS was unaltered by PYR but the apparent volume of distribution was significantly increased from a mean of 1.53 1 kg-1 to 1.93 1 kg-1 and the peak DDS plasma levels measured fell by 17%. 4 The pharmacokinetic parameters of PYR were unchanged by DDS. 5 The half-life of MADDS was unchanged by PYR and was not affected by the acetylator status of the subject. 6 Salivary DDS excretion reflects the free plasma DDS concentration. Administration of PYR with DDS significantly alters the mean saliva/plasma DDS ratio from 0.265 to 0.358 suggesting an increase in free DDS with PYR therapy. 7 In vitro studies of plasma protein DDS binding indicate that DDS binds to a single class of binding sites on human plasma protein and PYR competitively displaces DDS from these sites. 8 The usefulness of salivary drug measurements in detecting increases of free drug in plasma in man is demonstrated.

Adult↗
PubMed1984

A rapid method for determination of acetylation phenotype using dapsone.

A rapid, simple one-stage protein precipitation method for the estimation of plasma dapsone (DDS) and monoacetyldapsone (MADDS) concentration by high-pressure liquid chromatography (h.p.l.c.) is described. Its performance in the assignment of acetylator phenotype was compared with a reference h.p.l.c. method utilising an extraction procedure and internal standard. The rapid h.p.l.c. technique combined with measurement of the plasma MADDS/DDS ratio is, in our opinion, the method of choice for the determination of the acetylator phenotype in population studies.

Acetylation↗
PubMed1986

The pharmacokinetics of dapsone after oral administration to healthy volunteers.

After oral administration of 100 mg dapsone (DDS) to 25 healthy volunteers peak serum DDS concentrations between 1.10 and 2.33 mg l-1 were reached within 0.5 to 4 h. AUCs varied from 20.3 to 75.4 mg l-1 h, while the elimination half-lives ranged from 11.5 to 29.2 h. The apparent volumes of distribution were 0.84 to 1.26 l kg-1 body weight, assuming complete bioavailability. Statistically significant differences in peak drug concentration, peak time and AUC existed between males and females. Absorption and elimination of DDS appeared to be faster than reported in other studies, suggesting differences in DDS kinetics between healthy volunteers and patients.

Acetylation↗
PubMed1986

Excretion of chloroquine, dapsone and pyrimethamine in human milk.

The concentration of chloroquine (CQ), dapsone (DDS) and pyrimethamine (PYR) in plasma and milk were measured following the coadministration of a single dose of chloroquine and Maloprim to lactating women. The milk to plasma area under the concentration-time curve (AUC) ratio ranged from 1.96 to 4.26 for CQ, 0.22 to 0.45 for DDS and 0.46 to 0.66 for PYR. Assuming a daily milk ingestion of 1 l by the infant, the maximum percentage of the maternal dose for CQ, DDS and PYR in milk was 4.2%, 14.3% and 45.6%, respectively, over a 9 day period.

Adult↗
PubMed1987

Influence of age, sex and body weight on the dapsone acetylation phenotype.

The acetylation of dapsone (DDS) was determined by estimation of the ratio of monoacetyldapsone (MADDS) to DDS concentrations in plasma following a single dose of DDS in 337 white British subjects (193 female; 144 male). The percentage of slow DDS acetylators in the whole group was 60.3%. There was no statistically significant difference in this proportion between 191 elderly subjects (age greater than 65 years) and 143 young subjects (age less than 30 years). Although there was a small (66.3%) but significant (P = 0.033) preponderance of slow acetylators in the young male group there was no difference in the distribution of acetylator phenotypes between the sexes among either the elderly group or in the whole population studied. No correlation was found between absolute body weight and MADDS/DDS ratios.

Acetylation↗
PubMed1988

N-acetylation phenotyping with dapsone in a mainland Chinese population.

1 The N-acetylation of dapsone (DDS) was studied in 108 unrelated Chinese subjects residing in the mainland of China. 2 The frequency of slow acetylators determined using the plasma monoacetyldapsone to DDS ratio (MADDS/DDS, slow acetylators less than 0.30 and rapid acetylators greater than 0.35) at 3 h after an oral dose of DDS (100 mg) was 13.0% (14 of the 108 subjects) with a 95% confidence interval of 7.9 to 20.6%. 3 The mean plasma concentration of MADDS was about three times lower in the slow than in the rapid acetylators and there was a highly significant correlation (rs = 0.886, P less than 0.001) between plasma MADDS concentration and acetylation ratio. 4 Urinary acetylation ratios (MADDS/DDS) and cumulative urinary excretion of MADDS were significantly (P less than 0.001) lower in slow acetylators compared with rapid acetylators. In addition, there was a significant relationship (rs = 0.510 to 0.718, P less than 0.001) between plasma and urinary acetylation ratios. However, the distribution of the urinary acetylation ratio was not bimodal. 5 The urinary acetylation ratio after an oral dose of DDS is not a discriminative index for determining acetylation phenotype.

Acetylation↗
PubMed1988

N-acetylation polymorphism of dapsone in a Japanese population.

1. The N-acetylation of dapsone (DDS) was studied in 182 unrelated healthy Japanese subjects. The frequency of slow acetylators determined using the plasma monoacetyldapsone (MADDS) to DDS ratio (MADDS/DDS, slow acetylators less than 0.30 and rapid acetylators greater than 0.35) at 3 h after an oral dose of DDS (100 mg) was 6.6% (12 of the 182 subjects) with a 95% confidence interval of 3.8 to 11.2%. 2. The frequency distribution histogram of the plasma MADDS/DDS ratio showed an apparent trimodal pattern. However, the numbers of heterozygous (n = 105) and homozygous rapid acetylators (n = 65) derived from the observed data did not agree with those predicted for the respective rapid acetylators (n = 70, and n = 100) by applying the Hardy-Weinberg Law, when the suggested antimode of 0.85 discriminating these two rapid acetylators was employed. 3. The incidence of slow acetylators was unexpectedly lower in the males (1.4%, 1 of the 69 subjects, with a 95% confidence interval of 0.2 to 7.7%) compared with the incidence in the females (9.7%, 11 of the 113 subjects, with a 95% confidence interval of 5.5 to 16.6%). The difference reached a marginally significant level (Fisher's exact probability test, P = 0.02). 4. The mean plasma concentration of MADDS was significantly (P less than 0.001) lower in the slow compared to the rapid acetylators and there was a highly significant correlation (rs = 0.757, P less than 0.001) between plasma MADDS levels and MADDS/DDS ratios. 5. Slow acetylators showed a significantly (P less than 0.001) lower urinary MADDS/DDS ratio and excreted less (P less than 0.001) MADDS than rapid acetylators.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylation↗
PubMed1989

Bioactivation of dapsone to a cytotoxic metabolite by human hepatic microsomal enzymes.

1. Using human mononuclear leucocytes as target cells, we have investigated the bioactivation of dapsone (DDS) to a cytotoxic metabolite in the presence of microsomes from nine human livers. Values for NADPH dependent toxicity ranged from 8.8-27% (15.8 +/- 5.9%) and were similar to those for microsomes from control mice, 16-24% (19.0 +/- 4.8%). 2. Microsomes prepared from mice induced with either phenobarbitone or beta-naphthoflavone did not produce significantly more NADPH dependent toxicity than microsomes prepared from control mice. 3. Cytotoxicity was abolished not only by ascorbic acid, but also by sub-physiological concentrations of N-acetylcysteine and glutathione. 4. DDS was metabolised in vitro to a hydroxylamine (metabolic conversion 3.1 +/- 1.5%), which was oxidised further to a cytotoxic metabolite which also became irreversibly bound to protein.

Adolescent↗