Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: antibacterials for systemic use, ATC code: J01FA02 
Spiramycin is an antibacterial antibiotic of the macrolide group.

ANTIBACTERIAL SUSCEPTIBILITY TESTING
The MIC breakpoints differentiating susceptible strains from intermediate strains, and intermediate strains from resistant strains are as follows:
S <1 mg/L and R >4 mg/L

The prevalence of acquired resistance in certain species may vary geographically and over time. It is therefore useful to have information on the prevalence of local resistance, especially when treating severe infections.

These data are only guidelines indicating the probability of susceptibility of a bacterial strain to this antibiotic.

When the variability of prevalence of resistance is known for a given bacterial species in France, it is indicated in the following table:


Category                                Incidence of acquired resistance in France (> 10%) (range)
SUSCEPTIBLE SPECIES

Gram positive aerobes
Bacillus cereus
Corynebacterium diphtheriae
Enterococci                             50% – 70%
Rhodococcus equi
Methicillin-sensitive staphylococcus
Methicillin-resistant staphylococcus*   70 – 80%
Streptococcus B
Unclassified Streptococcus              30 – 40%
Streptococcus pneumoniae                35 – 70%
Streptococcus pyogenes                  16 - 31%

Gram negative aerobes
Bordetella pertussis
Branhamella catarrhalis
Campylobacter
Legionella
Moraxella
Anaerobes
Actinomyces
Bacteroides                             30 – 60%
Eubacterium
Mobilincus
Peptostreptococcus                      30 – 40%
Porphyromonas
Prevotella
Propionibacterium acnes

Other
Borrelia burgdorferi
Chlamydia
Coxiella
Leptospires
Mycoplasma pneumoniae
Treponema pallidum


MODERATELY SUSCEPTIBLE SPECIES
(in vitro intermediate susceptibility)

Gram negative aerobes
Neisseria gonorrhoeae
Anaerobes
Clostridium perfringens

Others
Ureaplasma urealyticum

RESISTANT STRAINS
Gram positive aerobes
Corynebacterium jeikeium
Nocardia asteroides

Gram negative aerobes
Acinetobacter
Enterobacteria
Haemophilus
Pseudomonas

Anaerobes
Fusobacterium
Others
Mycoplasma hominis

Spiramycin has in vitro and in vivo activity on Toxoplasma gondii.

* The incidence of methicillin resistance is approximately 30 to 50% for all staphylococci and is mainly found in the hospital setting.

Pharmacokinetic Properties

5.2. Pharmacokinetic properties

Absorption
Absorption of spiramycin is rapid but incomplete. Food has no effect on absorption.
Distribution
After oral administration of 6 MIU of spiramycin, the peak serum concentration is 3.3 microgram/mL.
The plasma half-life is close to 8 hours.

Spiramycin does not pass into the CSF. It is excreted in breast milk.
The medicinal product is poorly bound to plasma protein (10%).

Spiramycin is very well distributed in saliva and tissue (lungs: 20 - 60 microgram/g; tonsils: 20 - 80 microgram/g; infected sinuses: 75-110 microgram/g; bone: 5-100 microgram/g).

Ten days after treatment discontinuation, 5 to 7 microgram/g of active substance remains in the spleen, liver and kidneys.

Macrolides penetrate and accumulate in phagocytes (neutrophils, monocytes, peritoneal and alveolar macrophages).
Intraphagocyte concentrations are high in humans.
These properties account for the effect of macrolides on intracellular bacteria.
Biotransformation
Spiramycin is metabolised in the liver, resulting in the formation of chemically unknown though active metabolites.

Elimination
- Urine: 10% of the ingested dose.
- Biliary excretion is very high, i.e., 15 to 40 times higher than serum concentrations.
- Appreciable amounts of spiramycin can be found in the faeces.