Novelties in the multifaceted miconazole effects on skin disorders.
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.


METHODS
Review of the current peer-reviewed publications.


CONCLUSIONS
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.
Quatresooz
Pascale
P
University Hospital of Liège, Department of Dermatopathology, B-4000 Liège, Belgium. Gerald.pierard@ulg.ac.be
Vroome
Valérie
V
Borgers
Marcel
M
Cauwenbergh
Geert
G
Piérard
Gérald E
GE
D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use; D000935:Antifungal Agents / Q000494:pharmacology / Q000627:therapeutic use*; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects / Q000378:metabolism; D003881:Dermatomycoses / Q000188:drug therapy* / Q000382:microbiology; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy / Q000382:microbiology; D006801:Humans; D008825:Miconazole / Q000494:pharmacology / Q000627:therapeutic use*; D017192:Skin Diseases, Bacterial / Q000188:drug therapy / Q000382:microbiology; D058886:Sterol 14-Demethylase
D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; C548418:CYP51A1 protein, human; D008825:Miconazole; D003577:Cytochrome P-450 Enzyme System; D058886:Sterol 14-Demethylase