A Phase 2, Controlled, Dose-Ranging Study of SB208, an Investigational Topical Nitric Oxide-Releasing Drug, for the Treatment of Tinea Pedis.

BACKGROUND: Tinea pedis, or athlete's foot, is a superficial, skin infection caused by dermatophytes. It is usually topically treated. Nitric oxide is endogenously produced in humans and has a variety of physiologic and antimicrobial properties. SB208 is a novel topical treatment comprising berdazimer sodium (a nitric oxide-storing macromolecule) and a hydrogel. Admixing these two components releases nitric oxide to the application site. METHODS: A phase 2, double-blind, randomized trial evaluated the safety and efficacy of 3 doses of SB208 (2%, 4%, and 16%) vs matching vehicle, administered once daily for 14 days, in subjects with culture-confirmed interdigital tinea pedis. The primary efficacy outcome was the proportion of subjects with negative fungal cultures at end of treatment (day 14). Secondary outcomes at days 14 and 42 were the proportion of subjects with mycological cure (negative potassium hydroxide wet mount skin test and culture), clinical cure (reduced signs and symptoms from baseline graded on a 4-point scale). Safety was monitored through physical examinations, adverse events, and hemoglobin and methemoglobin levels. Efficacy outcomes were analyzed using a two-sided Cochran-Mantel-Haenszel test for general association, stratified by site. RESULTS: At day 14, a higher proportion of patients had negative fungal cultures in the pooled SB208-treated group (62%; P=0.04) than the vehicle-treated group (43%). Of SB208 groups, the 4% group had higher incidence of negative fungal cultures vs the vehicle group (67.6% vs 42.9%; P=0.03). At day 42, pooled SB208-treated groups had significantly more mycological cure vs vehicle group (47% vs 31%, respectively; P=0.08), and clinical cure was maintained in 23% of pooled SB208-treated patients vs 14% of vehicle-treated patients. No safety concerns were reported. Adverse events were mild, not serious, and considered unrelated to study medications. CONCLUSIONS: Topical SB208 was effective and well tolerated in the treatment of tinea pedis. J Drugs Dermatol. 2018;17(8):888-893.

Cholesterol, cancer, and rebooting a treatment for athlete's foot.

A key enzyme in cholesterol synthesis is placed firmly on the oncogenic map and demonstrated to be a potential therapeutic target in liver cancer by repurposing a common antifungal agent (Liu et al, this issue).

Statistically designed nonionic surfactant vesicles for dermal delivery of itraconazole: characterization and in vivo evaluation using a standardized Tinea pedis infection model.

The study aims to statistically develop a hydrogel of itraconazole loaded nonionic surfactant vesicles (NSVs) for circumventing the shortcomings and adverse effects of currently used therapies. Influential factors were screened using first-order Taguchi design, thereafter, optimization was performed via D-optimal design involving screened factors (surfactant type, content and molar ratio of cholesterol: surfactant). Response variables investigated were percent drug entrapment, vesicle size, drug skin retention and permeation in 6h. Suspensions of NSVs were gelled to improve topical applicability. Characterization of formulations was performed using vesicle shape, size, surface charge, texture analysis and rheology behavior. Ex vivo studies in rat skin depicted that optimized formulation augmented drug skin retention and permeation in 6h than conventional cream and oily solution of itraconazole. Standardized Tinea pedis model in Wistar rats exhibited in vivo antifungal efficacy of optimized formulation, observed in terms of physical manifestations, fungal-burden score and histopathological profiles. Also, a unique investigation involving studying local oxidative stress of infected paw skins as an indicator of fungal infection was performed. Rapid alleviation of infection in animals treated with optimized hydrogel was observed in comparison to commonly prescribed therapies. Therefore, the optimized NSVs may be a promising and efficient alternative to available antifungal therapies.

Local oxidative stress in interdigital tinea pedis.

Several skin diseases are believed to be associated with oxidative stress. Tinea pedis is an infection of the feet caused by fungi. The infectious diseases caused by dermatophytes are mainly related to the enzymes produced by these fungi. The cutaneous oxidative stress status of tinea pedis has not been demonstrated in the published work up to now. The aim of the present study was to evaluate the role of oxidative stress in affected skin areas in a group of patients with interdigital tinea pedis. Thirty-one consecutive patients with a diagnosis of unilateral interdigital tinea pedis were enrolled. The samples were obtained by scraping the skin surface. Oxidative stress biomarkers such as superoxide dismutase, catalase and malondialdehyde levels were measured spectrophotometrically. The activities of superoxide dismutase and catalase and the levels of malondialdehyde were significantly higher on the lesional area than the non-lesional area (P < 0.001). According to sex and fungal subtypes, there was no significant difference in the levels of oxidative stress biomarkers in patients with tinea pedis (P > 0.05). Our results suggested that antioxidant defense of lesional skin surface was higher compared to non-lesional skin. This is possibly due to a compensatory response to various fungal infections and thereby protects the cells against oxidative damage.

Pharmacokinetic investigation of oral itraconazole in stratum corneum level of tinea pedis.

In the present study, the authors administered 100 mg itraconazole (ITCZ) twice daily for a period of 1 week to six patients with hyperkeratotic type tinea pedis, and examined its efficacy, safety profile, and usefulness. ITCZ concentration in stratum corneum was also measured to examine the mobility of the drug into the affected site of planta pedis. ITCZ concentration in the stratum corneum of the affected part was first detected at 1 week after the completion of administration, gradually increased over time, and peaked at 3 weeks, with the sum of ITCZ and hydroxyitraconazole (OH-ITCZ) amounting to 163.7 ng g(-1) on a average. It then gradually decreased to a total sum of 10.3 ng g(-1) on average at 8 weeks following the completion of administration. When compared with the geometric mean minimum inhibitory concentration (MIC) of ITCZ against fresh clinical isolates of dermatophytes (Trichophyton rubrum) (0.06 microg ml(-1)), the stratum corneum ITCZ concentration in this study was 2.1-fold of the geometric mean MIC at 2 weeks following the completion of administration, and 2.4-fold at 4 weeks. Although ITCZ does not produce therapeutic effectiveness (fungistasis) during the period of administration, it starts appearing at 2 weeks after the completion of administration, and after it peaks out at 3-4 weeks, clinical symptoms started improving. These results suggest that satisfying effects can be achieved in a short-term oral ITCZ at a dose of 100 mg twice daily for a period of 1 week in cases of hyperkeratotic type tinea pedis.

[Oxygen-dependent phagocytosis in patients with tinea pedis during treatment]. / Oksigenozavisimyi fagotsitoz u bol'nykh rubrofitiei stop v protsesse lecheniia.

Clinico-cytochemical (with the use of NBT test) studies of 27 patients with T. rubrum-induced trichophytosis of the soles has demonstrated a functional imbalance of the peripheral blood phagocytizing cells. Reduced neutrophil activity is associated with a compensatory elevation of mononuclear fungicidal potential. Chlorophyllipt administration corrected the metabolic shifts.