Nitozol Mechanism of Action

Pharmacology: When ketoconazole 2% shampoo was applied dermally to intact or abraded skin of rabbits for 28 days at doses up to 50 mg/kg and allowed to remain 1 hr before being washed away, there were no detctable plasma ketoconazole levels using an assay method having a lower detection limit 5 ng/mL.
Nitozol was not detected in plasma in 39 patients who shampooed 4-10 times/week to 6 months or in 33 patients who shampooed 2-3 times/week for 3-26 months (mean: 16 months). Twelve hours after a single shampoo, hair samples taken from 6 patients showed that high amounts of ketoconazole were present on the hair but only about 5% had penetrated into the hair keratin. Chronic shampooing (twice weekly for 2 months) increased the ketoconazole levels in the hair keratin 20% but did not increase levels on the hair. There were no detectable plasma levels.
An exaggerated use washing test on the sensitive antecubital skin of 10 subjects twice daily for 5 consecutive days showed that the irritancy potential of ketoconazole 2% shampoo was significantly less than that of 2.5% selenium sulfide shampoo.
A human sensitization test, a phototoxicity study and a photoallergy study conducted in 38 male and 22 female volunteers showed no contact sensitization of the delayed hypersensitvity type, no phototoxicity and no photoallergenic potential due to Nitozol.
Mode of Action: Interpretations of in vitro studies suggests that ketoconazole impairs the synthesis of ergosterol, which is a vital component of fungal cell membranes. It is postulated that the therapeutic effect of ketoconazole in dandruff is due to the reduction of Pityrosporum ovale (Malassezia ovale), but this has not been proven. Support for this hypothesis comes from a 4-week, double-blind, placebo-controlled clinical trial, in which the decrease in P. ovale on the scalp was significantly greater with ketoconazole (36 patients) than with placebo (20 patients) and was comparable to that with selenium sulfide (42 patients). In the same study, ketoconazole and selenium sulfide reduced the severity of adherent dandruff significantly more than the placebo did.
Ketoconazole produced significantly higher proportions of patients with at least 50% reductions in adherent dandruff (50% versus 15%) and in loose dandruff (67% versus 15%) than did the placebo.
Microbiology: Nitozol is a broad-spectrum synthetic antifungal agent which inhibits the growth of the following common dermatophytes and yeasts by altering the permeability of the cell membrane: Dermatophytes: Trichophyton rubrum, T. mentagrophytes, T. tonsurans, Microsporum canis, M. audouini, M. gypseum and Epidermophyton floccosum; yeast: Candida albicans, C. tropicalis, Pityrosporum ovale (Malassezia ovale) and Pityrosporum orbiculare (M. furfur). Development of resistance by these microorganism to ketoconazole has not been reported.