Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1   Pharmacodynamic properties
Pharmacotherapeutic group: Antifungials for dermatoplogical use - Bifonazole: ATC Code: D01A C10
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.

Fluocinonide:
Topical corticosteroids share anti-inflammatory, anti-pruritic and vasoconstrictive actions.
The mechanism of anti-inflammatory activity of the topical corticosteroids is unclear.
Various laboratory methods, including vasoconstrictor assays, are used to compare and predict potencies and/or clinical efficacies of the topical corticosteroids. There is some evidence to suggest that a recognizable correlation exists between vasoconstrictor potency and therapeutic efficacy in man.

Pharmacokinetic Properties

5.2   Pharmacokinetic properties
Bifonazole 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.
Plasma levels up to 16ng/ml were obtained in babies with nappy rash after a single 5g application of the cream.
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.

Bifonazole 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).

Fluocinonide:
The extent of percutaneous absorption of topical corticosteroids is determined by many factors including the vehicle, the integrity of the epidermal barrier, and the use of occlusive dressings.
Topical corticosteroids can be absorbed from normal intact skin. Inflammation and/or other disease processes in the skin increase percutaneous absorption. Occlusive dressings substantially increase the percutaneous absorption of topical corticosteroids.
Thus, occlusive dressings may be a valuable therapeutic adjunct for treatment of resistant dermatoses.
Once absorbed through the skin, topical corticosteroids are handled through pharmacokinetic pathways similar to systemically administered corticosteroids.
Corticosteroids are bound to plasma proteins in varying degrees. Corticosteroids are metabolized primarily in the liver and are then excreted by the kidneys. Some of the topical corticosteroids and their metabolites are also excreted into the bile.