Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Anti-acne preparations for topical use – Anti-infectives for treatment of acne – Erythromycin

ATC code: D10AF02

The erythromycin contained in Aknemycin has a bacteriostatic effect on all germs that play a role in the development of acne, in particular Propionibacterium acnes (Corynebacterium acnes), Staphylococcus aureus and Staphylococcus epidermidis. This also includes inhibition of lipolysis of the sebum lipids.

Furthermore, erythromycin possesses a direct anti-inflammatory effect.

Spectrum of Activity of Erythromycin
The following spectrum of activity of erythromycin only includes in vitro data. This is therefore not necessarily associated with an assertion of the clinical efficacy of the active substance with respect to the pathogens, which are assessed as sensitive, intermediary or resistant.

Sensitivity
For the erythromycin base the following provisional minimum inhibitory concentrations (MIC) are proposed: for sensitive germs  1 mg/l, for germs of medium sensitivity (intermediary) 2 – 4 mg/l and for resistant germs  8 mg/l [limiting values (breakpoints) according to DIN 58 940]. Based on this procedure, too high resistance ratios result for topical application in cases of doubt because higher concentrations are achievable locally.

Table: In vitro Therapeutic Spectrum of Erythromycin [Expert Report dated 2003].

In vitro Data
Relevant pathogens with respect to the claimed       Lowest and highest ascertained value (range) for indication                                           the acquired resistance in Germany (%) Sensitive aerobic gram-positive
Staphylococcus aureus*                                    86.0 – 87.9 Staphylococcus epidermidis                                31.0 – 40.9 Sensitive anaerobic gram-positive
Propionibacterium acnes                                   88.6
Intermediary aerobic gram-positive
Staphylococcus aureus*                                    2.6 – 6.0 Staphylococcus epidermidis                                0.9 – 9.4 Intermediary anaerobic gram-positive
Propionibacterium acnes
Resistant aerobic gram-positive
Staphylococcus aureus*                                    7.8 – 11.1 Staphylococcus epidermidis                                58.2 – 62.4 Resistant anaerobic gram-positive
Propionibacterium acnes                                   11.4
* Methicillin-sensitive

The resistance ratios contained in the table with respect to systemically applicable erythromycin cannot simply be transferred to topical treatment. The sensitivity or resistance of a pathogen depends on the achievable concentration at the site of the desired effect. In individual cases of topical antibiotic application it is not known today how high the active substance concentration at the various locations of the desired effect really is. In the case of topical acne treatment it can be assumed that pathogens which have been classified as "non-resistant" according to the interpretation criteria for systemic therapy are recorded without difficulty. The question remains unanswered as to whether "resistant" bacteria can also be reached by the relatively high local concentrations. It is known that the populations of Staphylococcus aureus, Staphylococcus epidermidis and Propionibacterium acnes can display different levels of resistance on and in the skin of the same acne patient. The important factor for therapeutic success is not the entire elimination of all (including the "resistant") germs, but a clear reduction in the germ count.

The good clinical efficacy of Aknemycin in various forms of acne has been demonstrated in placebo-controlled, double-blind and open studies. Local antibiotic treatment with Aknemycin is comparable in terms of its efficacy with the systemic administration of antibiotics.

So far there have been no reports of photosensitisation resulting from the topical application of erythromycin.

The alcoholic base of the Aknemycin solution supports the antibacterial effect of the erythromycin and also dissolves the sebaceous matter.

Pharmacokinetic Properties

5.2   Pharmacokinetic properties

After the topical application of Aknemycin the active substance erythromycin is not absorbed percutaneously to any significant extent. Even after several weeks of the application of Aknemycin over a large area it was not possible to detect any erythromycin in the serum of the patients.