Metabolic, pharmacokinetic, and toxicological issues surrounding dapsone

Molinelli, Elisa; Paolinelli, Matteo; Campanati, Anna; Brisigotti, Valerio; Offidani, Annamaria

doi:10.1080/17425255.2019.1600670

Cited by 39 publications

(40 citation statements)

References 123 publications

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“…Despite systemic toxic levels, it seems that the amount of DAP retained in the skin (20 µg/mg skin) was not enough for parasite clearance, probably due to its accumulation in other skin layers and not in the dermis, according to the ex vivo permeability studies for the models of IS or TS. On the other hand, the plasma-binding protein described for DAP was around 70% [49], and as only the free drug is effective, this could be below the threshold of therapeutic efficacy. This estimation also considers that drug detected in the blood was through the dermis (the skin target), which only represented 1% of that total administered drug.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Skin Permeation and Retention of Topical Dapsone in Murine Cutaneous Leishmaniasis Lesions

et al. 2019

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The oral administration of dapsone (DAP) for the treatment of cutaneous leishmaniasis (CL) is effective, although serious hematological side effects limit its use. In this study, we evaluated this drug for the topical treatment of CL. As efficacy depends on potency and skin penetration, we first determined its antileishmanial activity (IC50 = 100 μM) and selectivity index in vitro against Leishmania major-infected macrophages. In order to evaluate the skin penetration ex vivo, we compared an O/W cream containing DAP that had been micronized with a pluronic lecithin emulgel, in which the drug was solubilized with diethylene glycol monoethyl ether. For both formulations we obtained similar low flux values that increased when the stratum corneum and the epidermis were removed. In vivo efficacy studies performed on L. major-infected BALB/c mice revealed that treatment not only failed to cure the lesions but made their evolution and appearance worse. High plasma drug levels were detected and were concomitant with anemia and iron accumulation in the spleen. This side effect was correlated with a reduction of parasite burden in this organ. Our results evidenced that DAP in these formulations does not have an adequate safety index for use in the topical therapy of CL.

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Section: Discussionmentioning

confidence: 99%

Evaluation of Skin Permeation and Retention of Topical Dapsone in Murine Cutaneous Leishmaniasis Lesions

et al. 2019

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“…Dapsone prevents neutrophil chemotaxis via IL8 67 ; there are publications suggesting that increase of IL8 and increase of neutrophils can be controlled with dapsone in ARDS (acute respiratory distress syndrome) cases related to COVID‐19 68 …”

Section: Infection Risk In Immunomodulators and Immunosuppressants Usmentioning

confidence: 99%

Immunosuppressive and immunomodulator therapy for rare or uncommon skin disorders in pandemic days

Karadağ

Kayıran

Lotti

et al. 2020

Dermatologic Therapy

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Immunosuppressive and immunomodulatory therapies are important in dermatology, but indications are influenced by SARS-CoV-2. We will focus on skin disorders such as autoimmune connective tissue disorders, neutrophilic dermatoses, and vasculitis. Immunomodulators such as colchicine and antimalarials can easily be preferred taking their beneficial effects on COVID-19 into consideration and also given their wide spectrum of action. Among the conventional therapies, methotrexate, azathioprine, and mycophenolate mofetil increase the risk of infection, and thus their use is recommended only when necessary and at low doses. On the other hand, use of cyclosporine is also not recommended as it increases the risk of hypertension, which is susceptible to COVID-19. Anti-TNF agents from among the biological therapies appear to be slightly risky in terms of susceptibility to infection. However, there are ongoing studies which suggest that some biological treatments may reduce cytokine storm impeding the COVID-19 progression as a result, in spite of their susceptibilities to COVID-19. Patients, who will be started on immunosuppressive therapy, should be tested for COVID-19 prior to the therapy, and in the event that COVID-19 is suspected, the therapy should be discontinued.

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“…Dapsone, a sulfone antibiotic, has been used since the 150's to treat Mycobacterial disease and other infections including Pneumocystis, Plasmodia and others. 25,26,40 It is on the WHO list of essential medicines. By virtue of dapsone's ability to inhibit neutrophils' chemotaxis to sites of inflammation, dapsone has seen wide dermatologic use in treating neutrophilic dermatoses.…”

Section: Dapsonementioning

confidence: 99%

“…44 They furthermore demonstrated this effect was mediated by dapsone inhibition of the neutrophil respiratory burst. 44 After 100 mg of oral dapsone serum concentrations between 1 and 2 mg/L are seen after 1 to 4 h. Half-life varies, from 12 to 30 h. 40 A usual dose on the higher end would be 100 mg q 12 h.…”

Section: Dapsonementioning

confidence: 99%

Dapsone as treatment adjunct in ARDS

Kast¹

2020

Experimental Lung Research

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Multiple pharmacological interventions tested over the last decades have failed to reduce ARDS mortality. This short note recounts past data indicating that (i) neutrophils home along an IL-8 gradient, (ii) in ARDS, massive neutrophil accumulation and degranulation in and along bronchoalveolar spaces contributes to damage and hypoxia, (iii) large increases in IL-8 are one of the chemotaxic signals drawing neutrophils to the ARDS lung, and (iv) old data from dermatology and glioblastoma research showed that the old drug against Hansen's disease, dapsone, inhibits neutrophils' chemotaxis to IL-8. Therefore dapsone might lower neutrophils' contributions to ARDS lung pathology. Dapsone can create methemoglobinemia that although rarely problematic it would be particularly undesirable in ARDS. The common antacid drug cimetidine lowers risk of dapsone related methemoglobinemia and should be given concomitantly. ARTICLE HISTORY

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Metabolic, pharmacokinetic, and toxicological issues surrounding dapsone

Cited by 39 publications

References 123 publications

Evaluation of Skin Permeation and Retention of Topical Dapsone in Murine Cutaneous Leishmaniasis Lesions

Evaluation of Skin Permeation and Retention of Topical Dapsone in Murine Cutaneous Leishmaniasis Lesions

Immunosuppressive and immunomodulator therapy for rare or uncommon skin disorders in pandemic days

Dapsone as treatment adjunct in ARDS

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