Clinical ReviewDapsone and sulfones in dermatology: Overview and update☆
Section snippets
Chemistry of sulfones
Dapsone (4-4′-diaminodiphenylsulfone, DDS) is structurally the simplest of the sulfones, all of which share the characteristic structure: a sulfur atom linking to two carbon atoms (Fig 1).
Absorption
Orally ingested dapsone is absorbed readily from the gastrointestinal tract with bioavailability of more than 86%.19 Absorption is reduced in severe leprosy.20 The disubstituted sulfones, such as sulfoxone, are poorly absorbed after oral administration, and large amounts are excreted in the feces.21 In healthy volunteers, after 100 mg of oral dapsone, peak serum dapsone concentrations between 1.10 and 2.33 mg/L were reached within 0.5 to 4 hours.22 The elimination half-life ranged from 12 to 30
Antimicrobial action
As an antibiotic, dapsone acts in the same way as sulfonamides, inhibiting the synthesis of dihydrofolic acid through competition with para-aminobenzoate for the active site of dihydropteroate synthetase.45 Therefore dapsone inhibits the growth of microorganisms that are dependent on endogenous folic acid synthesis.
Anti-inflammatory action
Dapsone is effective in dermatoses with abnormal neutrophil accumulation, through many potential mechanisms. Dapsone interferes with neutrophil chemotactic migration46 and β2
Clinical indications
Dapsone is both an antibiotic and an anti-inflammatory agent. It is bacteriostatic against Mycobacterium leprae and is an essential component of leprosy treatment. It has also been used successfully to treat actinomycetoma,64, 65, 66 in prophylaxis and treatment of Pneumocystis carinii pneumonia (PCP),67, 68, 69 and for malaria.70
As an anti-inflammatory agent, dapsone has been used to treat many skin diseases characterized by the abnormal infiltration of neutrophils or eosinophils, such as
Adverse effects
Overall, the risk of dapsone-dependent side effects is very low if the plasma concentration is below 5 mg/L.24 Although the therapeutic range for leprosy was estimated to be 0.5 to 5 mg/L, the ranges for other indications are not known. Metabolism of dapsone by cytochrome P-450 to hydroxylamines is responsible for some dapsone side effects including methemoglobinemia, hemolysis, and fatal agranulocytosis, but the mechanism by which hydroxylamines cause these side effects is unclear (Table III).
How to increase tolerance to dapsone
Use of a metabolic inhibitor such as cimetidine to reduce hepatic oxidation of dapsone to hydroxylamine has successfully decreased its adverse effects.181 Methemoglobin formation in the presence of cimetidine was maintained at 30% below control levels for almost 3 months, and the incidence of reported side effects such as headache and lethargy were significantly reduced.182 Long-term concurrent cimetidine administration increased plasma dapsone levels without increased hemolysis and reduced
Use during pregnancy and lactation
Pregnancy may be a trigger of leprosy and other dermatologic diseases because of the changes in cell-mediated and humoral immunity during gestation.186, 187 First appearance of leprosy, reactivation of the disease, and relapse in “cured” patients are likely to occur particularly in the third trimester of pregnancy.188 Because up to 20% of children born to mothers with leprosy may experience leprosy by puberty,188 pregnant women with leprosy require treatment.
Treatment with dapsone for various
Drug interactions
Drugs that affect the pharmacokinetics and efficacy of dapsone are listed in Table V.
Names of drugs Effects on dapsone Trimethoprim Increases plasma concentration and adverse effects of dapsone248 Rifampin Induces dapsone metabolism by causing a proliferation of the smooth endoplasmic reticulum and an increase of cytochrome P-450 content in the liver249; also enhances urinary excretion of dapsone250 Pyrimethamine (together with dapsone as Maloprim) Increases
References (252)
- et al.
The treatment of streptococcal infections in mice with 4:4′-diaminodiphenyl sulfone
Lancet
(1937) - et al.
Dermatitis herpetiformis
Clin Gastroenterol
(1974) - et al.
Inhibition of dapsone excretion by probenecid
Lancet
(1969) - et al.
Dapsone suppresses integrin-mediated neutrophil adherence function
J Invest Dermatol
(1992) - et al.
Inhibition of the human leukocyte enzymes myeloperoxidase and eosinophil peroxidase by dapsone
Biochem Pharmacol
(1992) - et al.
Mechanisms by which clofazimine and dapsone inhibit the myeloperoxidase system: a possible correlation with their anti-inflammatory properties
Biochem Pharmacol
(1991) - et al.
Mechanism of inhibition of myeloperoxidase by anti-inflammatory drugs
Biochem Pharmacol
(1991) - et al.
Dapsone inhibits LTB4 binding and bioresponse at the cellular and physiologic levels
Eur J Pharmacol
(1988) - et al.
Inhibition of rat mast cell arachidonic acid cyclooxygenase by dapsone
J Allergy Clin Immunol
(1983) - et al.
Inhibition of the release of prostaglandins, leukotrienes and lysosomal acid hydrolases from macrophages by selective inhibitors of lecithin biosynthesis
Biochem Pharmacol
(1983)
Inhibition of neutrophil adherence to antibody by dapsone: a possible therapeutic mechanism of dapsone in the treatment of IgA dermatoses
J Invest Dermatol
A controlled trial of dapsone versus pyrimethamine-sulfadoxine for primary prophylaxis of Pneumocystis carinii pneumonia and toxoplasmosis in patients with AIDS
Biomed Pharmacother
Leprosy
Lancet
Randomized trial of dapsone and aerosolized pentamidine for the prophylaxis of Pneumocystis carinii pneumonia and toxoplasmic encephalitis [see comments]
Am J Med
Aerosolized pentamidine as pneumocystis prophylaxis after bone marrow transplantation is inferior to other regimens and is associated with decreased survival and an increased risk of other infections
Biol Blood Marrow Transplant
Immunofluorescence studies in the diagnosis of dermatitis herpetiformis and its differentiation from bullous pemphigoid
J Invest Dermatol
Derivate des p-nitrophenols
Ber deutsch Chem Ges
Action anti-streptococcique des derives sulfures organiques
Compt Rendu Acad Sci
Note preliminaire surl'action de la pare-diacetyl-aminodiphenyl sulfone (1399F) dans la blennorrhagic
Bull Soc Fr Dermatol Syphilol
Influence of promin, starch, and hepataldehyde on experimental leprosy in rats
Arch Pathol
Effect of promin (sodium salt of p,p′-diaminodiphenyl-sulfone-N-′didextrose sulfate) on experimental tuberculosis: preliminary report
Proc Staff Meet Mayo Clinic
The promin treatment of leprosy
Public Health Rep
Two-and-a-half years' experimental work on the sulphone group of drugs
Lepr Rev
The story of sulfones in tropical medicine and dermatology
Int J Dermatol
Acerca da accao das sulfamidas e das sulfonas na doenca de Duhring
Trab Soc Portuguesa Dermatol Venereol
The treatment of dermatitis herpetiformis
Clin Exp Dermatol
Fine points in the management of dermatitis herpetiformis
Semin Dermatol
Dermatitis herpetiformis: a review of fifty-four patients
Ir J Med Sci
Childhood dermatitis herpetiformis: an unusual presentation
Clin Exp Dermatol
Oral lesions in dermatitis herpetiformis
Br J Dermatol
Subcorneal pustular dermatosis
Br J Dermatol
Dapsone—other indications
Int J Dermatol
The absolute oral bioavailability of dapsone in dogs and humans
Int J Clin Pharmacol Ther Toxicol
Clinical pharmacokinetic considerations in the treatment of patients with leprosy
Clin Pharmacokinet
The disposition of sulfoxone and solasulfone in leprosy patients
Lepr Rev
The pharmacokinetics of dapsone after oral administration to healthy volunteers
Br J Clin Pharmacol
Combinations involving dapsone, rifampin, clofazimine, and ethionamide in the treatment of M. leprae infections in mice
Int J Lepr Other Mycobact Dis
Clinical pharmacokinetics of dapsone
Clin Pharmacokinet
Pharmacokinetics of dapsone administered daily and weekly in human immunodeficiency virus-infected children
Antimicrob Agents Chemother
Penetration of dapsone into cerebrospinal fluid of patients with AIDS
J Antimicrob Chemother
Excretion of chloroquine, dapsone and pyrimethamine in human milk
Br J Clin Pharmacol
Noninvasive tests of CYP3A enzymes
Pharmacogenetics
N-Hydroxylation of dapsone by multiple enzymes of cytochrome P450: implications for inhibition of haemotoxicity
Br J Clin Pharmacol
Evidence that the biotransformation of dapsone and monoacetyldapsone to their respective hydroxylamine metabolites in rat liver microsomes is mediated by cytochrome P450 2C6/2C11 and 3A1
Drug Metab Dispos
Metabolism of dapsone to its hydroxylamine by CYP2E1 in vitro and in vivo
Clin Pharmacol Ther
CYP2C8/9 mediate dapsone N-hydroxylation at clinical concentrations of dapsone
Drug Metab Dispos
Effects of ketoconazole on the erythromycin breath test and the dapsone recovery ratio [letter]
Br J Clin Pharmacol
Frequency distribution of dapsone N-hydroxylase, a putative probe for P4503A4 activity, in a white population
Clin Pharmacol Ther
Polymorphic acetylation of the antibacterials sulfamethazine and dapsone in South Indian subjects
Am J Trop Med Hyg
Acetylator phenotype and the effect of dapsone in rheumatoid arthritis
J Rheumatol
Cited by (388)
Chaulmoogra oil-based nanoemulsions for leprosy treatment: A case study with the dapsone
2023, Journal of Drug Delivery Science and TechnologyCatalyst-Free Electrochemical Sulfonylation of Organoboronic Acids
2023, Journal of Organic ChemistryAnalysis of whole blood protoporphyrin and plasma porphyrin in patients on dapsone
2024, Photodermatology Photoimmunology and PhotomedicinePersistent Papules in Erythema Elevatum Diutinum Treated With Dapsone: Answer
2024, American Journal of DermatopathologyLinear IgA Bullous Dermatosis in Korea Using the Nationwide Health Insurance Database
2024, Journal of Clinical MedicineEnantioselective sulfonylation to construct 3-sulfonylated oxindoles
2024, Chemical Communications
- ☆
Reprint requests: Matthew J. Stiller, MD, Department of Dermatology, New York-Presbyterian Medical Center, 161 Fort Washington Ave, New York, NY 10032.