Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1. Pharmacodynamic Properties

Pharmacotherapeutic group: Anti-fungals for dermatological use – Bifonazole 
ATC Code: D01AC10

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. 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.

Pharmacokinetic Properties

5.2. Pharmacokinetic Properties

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.

After a single application (topical) of 15.2mg [14C] bifonazole cream, and subsequent occlusion for six hours, 0.6±0.3% of the dose was absorbed. The absorption rate was approximately 0.008mg/100cm2 per hour. In inflamed skin these values were higher by a factor of four. Similar results were obtained after the application of bifonazole as a 1% solution.
After intravenous administration of 0.016mg/kg [14C] bifonazole, tissue uptake was rapid. Bifonazole is, however, rapidly metabolised with only 30% of an intravenous dose remaining unaltered 30 minutes post-dose.

Elimination
Elimination of the metabolites is biphasic (T½ of eight and 50 hours). Within five days of administration 45% of the administered dose has been excreted renally, with 40% being eliminated via the liver and bile (faeces).