Onabet Mechanism of Action

Pharmacology: Mechanism of Action: Sertaconazole nitrate cream is an azole antifungal (see Microbiology as follows)
Pharmacokinetics: In a multiple dose pharmacokinetic trial that included 5 male subjects with interdigital tinea pedis (range of diseased area, 42-140 cm²; mean, 93 cm²), Sertaconazole nitrate cream, 2%, was topically applied every 12 hours for a total of 13 doses to the diseased skin (0.5 grams sertaconazole nitrate per 100 cm²). Sertaconazole concentrations in plasma measured by serial blood sampling for 72 hours after the thirteenth dose were below the limit of quantitation (2.5 ng/mL) of the analytical method used.
Nonclinical Toxicology: Carcinogenesis. Mutagenesis, Impairment of Fertility: In a rat dermal carcinogenicity study, topical administration of sertaconazole nitrate cream for up to 102 weeks did not increase the number of neoplastic lesions compared to control animals, at sertaconazole nitrate doses of up to 800 mg/kg/day (approximately 200 times the maximum recommended human dose based on a body surface area comparison).
No clastogenic potential was observed in a mouse micronucleus test. Sertaconazole nitrate was considered nonclastogenic in the in vivo mouse sister chromatid exchange assay. There was no evidence that sertaconazole nitrate induced unscheduled DNA synthesis in primary rat hepatocyte cultures.
At oral doses up to 60 mg/kg/day (16 times the maximum recommended human dose based on a body surface area comparison), sertaconazole nitrate exhibited no toxicity or adverse effects on reproductive performance or fertility in male or female rats.
Clinical Studies: In two randomized, double-blind, clinical trials, subjects 12 years and older with interdigital tinea pedis applied Sertaconazole nitrate cream, 2%, or vehicle, twice daily for four weeks. Subjects with moccasin-type (plantar) tinea pedis and/or onychomycosis were excluded from the trial. Two weeks after completion of therapy (six weeks after beginning therapy), subjects were evaluated for signs and symptoms related to interdigital tinea pedis. (See table.)

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In clinical trials, complete cure in sertaconazole treated subjects was achieved in 32 of 160 (20%) subjects with Trichophyton rubrum, in 7 of 28 (25%) subjects with Trichophyton mentagrophytes and in 1 of 13 (15%) subjects with Epidermophyton floccosum.
Microbiology: Mechanism of Action: Sertaconazole, an azole antifungal agent, inhibits fungal cytochrome P-450-mediated 14 alpha-lanosterol demethylase enzyme. This enzyme functions to convert lanosterol to ergosterol. Ergosterol is a key component of fungal cell membranes and lack of this component leads to fungal cell injury by leakage of key constituents in the cytoplasm from the cell.
Activity In Vitro and in Clinical Infections: Sertaconazole nitrate has been shown to be active against isolates of the following microorganisms in clinical infections (see Indications): Trichophyton rubrum; Trichophyton mentagrophytes; Epidermophyton floccosum.