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Novelties in the multifaceted miconazole effects on skin disorders.

Author(s): Quatresooz P, Vroome V, Borgers M, Cauwenbergh G, Pierard GE

Affiliation(s): University Hospital of Liege, Department of Dermatopathology, B-4000 Liege, Belgium. Gerald.pierard@ulg.ac.be

Publication date & source: 2008-08, Expert Opin Pharmacother., 9(11):1927-34.

Publication type: Research Support, Non-U.S. Gov't; Review

BACKGROUND: Miconazole nitrate is a time-honored antifungal of the imidazole class. OBJECTIVE: To revisit the various aspects of action of the drug in a dermatologic setting. METHOD: Review of the current peer-reviewed publications. RESULTS/CONCLUSION: Miconazole essentially inhibits 14alpha-demethylase, an enzyme required for the biosynthesis of ergosterol, which is the main sterol constituent of fungal cell membranes. Hence, toxic methylated sterols accumulate. Synthesis of triglycerides and phospholipids is also affected. In addition, miconazole also exhibits other ancillary mechanisms of action that probably participate in the therapeutic efficacy of the drug. The oxidative and peroxidative enzyme activities are altered leading to an intracellular build up of a toxic concentration of hydrogen peroxide. This may contribute to the deterioration of subcellular organelles and to cell necrosis. Farnesol synthesis is stimulated in Candida spp. leading to the prevention of yeast-to-mycelium formation. Overall, miconazole is fungistatic through its effect on ergosterol biosynthesis, but it may also have a fungicidal effect against a number of fungal species due to its effect on hydrogen peroxide accumulation. In addition, miconazole is active against a series of Gram-positive bacteria and has been shown to help the repair of the skin barrier function and to help mitigate some inflammatory cell reactions (such as in acne). To conclude, miconazole exerts multi-pronged effects both against pathogenic fungi and on skin physiology.

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