Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1. Pharmacodynamic Properties
Pharmacotherapeutic group: Antifungals for topical use – imidazole and triazole derivatives
ATC code : D01AC10

Mechanism of action
Bifonazole a broad-spectrum antifungal agent from the group of imidazole derivatives which act against dermatophytes, yeasts, moulds and other fungi such as Malassezia furfur. It is also effective against Corynebacterium minutissimum.
Bifonazole inhibits the biosynthesis of ergosterol at two different steps in the synthesis chain. This dual mechanism of action distinguishes bifonazole from other azole derivatives and from other antifungals agents. Inhibition of ergosterol synthesis leads to structural and functional impairment of the cytoplasmic membrane. Ergosterol is an essential component of the fungal cell membrane

Pharmacodynamic effects
Bifonazole exhibits significant fungicidal effects on dermatophytes, starting at concentrations of 5 μg/ml with an onset time of 6 hours. It is fungicidal against yeasts such as Candida species at concentrations of 20 μg/ml.
The active substance also has an inhibitory effect at concentrations 2-10 times lower than the MIC (minimum inhibitory concentration) values. The rapidly proliferating mycelium of Trichophyton mentagrophytes is inhibited even at a concentration of 3 μg/ml substrate.

Clinical efficacy and safety
Bifonazole shows a favourable resistance profile. Primary resistant variants of sensitive fungal species are very rare. Thus far, studies have not shown any evidence of a development of secondary resistance in primarily sensitive fungal strains.

Pharmacokinetic Properties

 5.2. Pharmacokinetic Properties
Absorption
Bifonazole penetrates well into infected skin layers.
Six hours after application, concentrations are measured that reach the MIC levels for the fungi involved in dermatomycoses or that exceed them by several orders of magnitude: from 1000 μg/cm3 in the top layer of the epidermis (stratum corneum) to 5 μg/cm3 in the stratum papillare.

The retention time of bifonazole solution in the skin, measured as the protective activity against infection, is 36-48 hours in guinea pigs.

The long retention time of bifonazole in the skin at effective antifungal concentrations and consideration of the type of fungicidal activity form the basis for single-dose application in local therapy. In absorption studies after topical application to intact human skin, the serum concentrations were always below the detection limit (<1 ng/ml); mild absorption was detected only in the event of inflamed skin. These extremely low drug concentrations (generally less than 5 ng/ml) mean that any systemic effect is not expected.