Nizoral Cream Mechanism of Action

Antifungal.
Pharmacology: Pharmacodynamics: Mechanism of action: Ketoconazole inhibits the biosynthesis of ergosterol in fungi and changes the composition of other lipid components in the membrane.
Pharmacodynamic effects: Usually ketoconazole cream acts rapidly on pruritus, which is commonly seen in dermatophyte and yeast infections, as well as skin conditions associated with the presence of Malassezia spp. This symptomatic improvement is observed before the first signs of healing are observed.
Pharmacokinetics: Plasma concentrations of ketoconazole were not detectable after topical administration of ketoconazole (Nizoral) 2% Cream in adults on the skin. In one study in infants with seborrheic dermatitis (n=19) where approximately 40 g of ketoconazole (Nizoral) 2% Cream was applied daily on 40% of the body surface area, plasma levels of ketoconazole were detected in 5 infants, ranging from 32 to 133 ng/mL.
Toxicology: Non-clinical information: Preclinical data reveal no special hazard for humans based on conventional studies including primary ocular or dermal irritation, dermal sensitization and repeat-dose dermal toxicity.
Acute dermal and ocular irritation studies with ketoconazole cream formulations in rabbits showed no dermal or ocular irritation. Results from a dermal sensitization study in guinea pigs showed no allergenic or sensitizing potential. In five repeat-dose dermal studies in rabbits, ketoconazole was administered to both abraded and non-abraded skin at a maximum dose of 40 mg/kg. In one study some slight irritation was noted in both the ketoconazole and placebo groups, however, in the remaining studies no dermal or systemic toxic effects were noted. Data from pharmacokinetic studies, of several topical formulations of ketoconazole under exaggerated test conditions in laboratory animals, showed no measurable ketoconazole plasma concentrations.
Microbiology: Ketoconazole, a synthetic imidazole dioxolane derivative, has a potent antimycotic activity against dermatophytes such as Trichophyton spp., Epidermophyton floccosum and Microsporum spp. and against yeasts, including Malassezia spp. and Candida spp. Especially the effect on Malassezia spp. is very pronounced.