Canespro Mechanism of Action

Pharmacotherapeutic group: Anti-fungals for dermatological use - Bifonazole. ATC Code: DD1AC10.
Pharmacology: Pharmacodynamics: Mode of action: Bifonazole is an imidazole derivative with a broad antimycotic spectrum, which includes dermatophytes, yeasts, moulds and other fungi such as Malassezia furfur. It is also effective against Corynebacterium minutissimum. Bifonazole exerts its anti-fungal action by inhibiting the biosynthesis of ergosterol on two different levels, thereby distinguishing bifonazole both from other azole derivatives and from other anti-fungals which act only on a single level. Inhibition of ergosterol synthesis leads to structural and functional impairment of the cytoplasmic membrane. The resistance situation for bifonazole is favorable. Primary resistant variants of sensitive fungal species are very rare. Investigations so far did not provide any evidence of a development of secondary resistance in primarily sensitive strains.
Pharmacokinetics: Absorption: Bifonazole penetrates well into infected skin layers. 6 hours after administration concentrations in the various skin layers reach from 1000 μg/cm³ in the top layer of the epidermis (stratum corneum) to 5 μg/cm³ in the stratum papillare. All concentrations determined are thus within a range of reliable antimycotic activity.
Toxicology: Preclinical safety data: Preclinical data reveals no special hazards for humans based on conventional studies of single dose toxicity and genotoxicity.
Effects on the liver (enzyme induction, fatty degeneration) were observed in repeated dose toxicity studies with oral administration but only at exposures in excess of the maximum human exposure indicating little relevance to clinical use. No carcinogenicity studies were performed with bifonazole. In reproduction toxicology studies in rabbits, oral doses of 30 mg/kg body weight resulted in embryotoxicity including lethality. In the rats, bifonazole at oral doses up to 100 mg/kg body weight was not embryotoxic, but a retarded skeletal development in the fetuses was observed at the dose of 100 mg/kg. This fetal effect on the skeletal development can be considered as a secondary effects resulting from the maternal toxicity (a reduction in body weight). Given the low absorption of the active ingredient via the skin these results have little relevance to clinical use. No impairment of male or female fertility was observed in rats at oral doses up to 40 mg/kg body weight. Bifonazole passes through the placental barrier in rats.