Two topical therapeutic agents were approved in Japan from 2015 to 2016, adding new options for onychomycosis therapy in the clinical field. In order to confirm the differences of formulation properties and nail pharmacokinetics between 5% luliconazole solution and 10% efinaconazole solution, drug concentration and antifungal activity in the nail were measured after topical treatment using human nail plates. In the in vitro permeation study, concentration of each drug was measured in the transversely sliced nail after single treatment with the two topical therapeutic agents. The results showed that concentration of luliconazole is higher than that of efinaconazole at all nail layers, differing by 1.7-8.4 times at each measurement point. Next, we examined antifungal activities of each drug in sliced nail after 14-day topical treatment. Mean rates of formation of inhibition zones for 5% luliconazole solution and 10% efinaconazole solution were 71.0% and 12.6%, respectively, and were statistically different. These results show that the two topical therapeutic agents have different properties, and suggest that 5% luliconazole solution has good nail permeation and retention characteristics. Moreover, luliconazole was found to retain enough antifungal activity in the nail plate against Trichophyton spp. after treatment with the topical agent.
There is not enough evidence available to guide wound care management in patients with Stevens-Johnson Syndrome (SJS)/ Toxic Epidermal Necrolysis (TEN). Current guidelines are based on expert opinion and mimic burn wound treatments, including the use of silverimpregnated dressings. Silver-containing dressings reduce the risk of invasive infection by minimizing the bacterial colonization of wounds. Evidence from small clinical trials in burn patients and a retrospective study in SJS/TEN patients indicate that they offer the advantage of not requiring daily dressing changes, which may damage the healing epidermis, and minimize patient discomfort. However, cytotoxic effects of silver have been demonstrated in human cell lines, including leukocytes. Studies investigating silver absorption from silvercoated dressings in burn patients have yielded conflicting results, with only a few case reports warning against the use of silver due to its cytotoxic effects. Systemic silver absorption in patients with SJS/TEN treated with any type of silver-based dressing has not been addressed in previous studies. We performed a retrospective chart review to investigate silver absorption in SJS/TEN patients treated with silver-nylon and silver-foam dressings. Six patients met inclusion/exclusion criteria, with body surface area (BSA) involvement of 75 %-100% and 5 to 25 % denuded skin. Five patients had elevated serum silver levels in the range of 9.9 to 110 ug/l, and had a decrease in leukocyte counts compared to baseline. The patient with normal serum silver levels had normal leukocyte counts, but developed transaminitis. None of the patients developed argyria. Our study indicates that silver-nylon and silver-foam dressings used in patients with SJS/TEN lead to systemic silver absorption. Whether the observed leukopenia and transaminitis are a result of either silver toxicity, the underlying hematological malignancy (3 patients), or SJS/TEN itself, our observations support the need to further investigate the safety of silver-based dressings in patients with SJS/TEN.
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