Clinical Drug Experience Knowledgebase

Sulconazole (trade name Exelderm) is an antifungal medication of the imidazole class. Sulconazole has a broad spectrum of antifungal activity in vitro and has been shown to be an effective topical antifungal agent for the management of superficial fungal infections of the skin, particularly dermatophytosis and tinea versicolor. Sulconazole inhibits the cytochrome P-450 isoenzyme, C-14-alpha-demethylase by binding to the heme iron of the enzyme. This results in a largely fungistatic effect. The selectivity of azole antifungal agents for pathogenic organisms compared with mammalian cells appears to depend on a preferred affinity of these drugs for fungal versus mammalian cytochrome P-450 sterol demethylases. Enzyme inhibition by sulconazole prevents the synthesis of ergosterol, a sterol found in fungal cell membranes but, in general, not in mammalian cell membranes. Additionally, lanosterol accumulates, which changes membrane permeability, cell volume, secondary metabolic effects, and causes defective cell division and growth inhibition. As sulconazole is primarily fungistatic, an intact immune system may be needed for infection resolution.In selected situations, sulconazole may have growth phase-dependent fungicidal activity against very susceptible organisms. The 1% concentration of sulconazole may greatly exceed the minimum inhibitory concentration and exert a direct physiochemical effect on the fungal cell membrane. The fungicidal effect may be due to hydrophobic interactions between sulconazole and unsaturated fatty acids in the membrane. Mammalian cells generally have little or no unsaturated fatty acids. Sulconazole may also prevent DNA and RNA synthesis and increase their degradation.Sulconazole has activity against many dermatophytes and yeast. One measure of the drug's antifungal activity is the relative inhibition factor (RIF). The RIF approaches 0% for a drug to which a fungus is highly sensitive and 100% for a drug that is non-inhibitory. The RIF values of sulconazole for Candida species, Aspergillus species, and dermatophytes are broadly similar to those of clotrimazole, econazole, ketoconazole, miconazole, and tioconazole. The mean RIF values were 69% (30—98%) for Candida species, 71% (61—82%) for Aspergillus species, and 12% (5—18%) for dermatophytes. Sulconazole is available as a cream or solution to treat skin infections such as athlete's foot, ringworm, jock itch, and sun fungus.   ^NCATS