Pharmacology: Azithromycin is the first of a subclass of macrolide antibiotics, known as azalides. The mode of action of azithromycin is inhibition of protein synthesis in bacteria by binding to the 50s ribosomal subunit and preventing translocation of peptides.
Azithromycin demonstrates activity in vitro against a wide range of bacteria including: Gram-positive Aerobic Bacteria: Staphylococcus aureus, Streptococcus agalactiae, Streptococcus pnemoniae, Streptococci (Group C, F, G), alpha-haemolytic streptococci (viridans group) and other streptococci, and Corynebacterium diphtheriae. Azithromycin demonstrates cross-resistance with erythromycin-resistant Gram-positive strains, including Streptococcus faecalis (enterococcus) and most strains of methicillin-resistant staphylococci. Macrolide-resistant Streptococcus pyogenes (group A beta-hemolytic streptococci).
Gram-negative Aerobic Bacteria: Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella catarrhalis, Acinetobacter species, Yersinia species, Legionella pneumophila, Bordetella pertussis, Bordetella parapertussis, Shigella species, Pasteurella species, Vibrio cholerae and parahaemolyticus, Plesiomonas shigelloides. Activities against Escherichia coli, Salmonella enteritidis, Salmonella typhi, Enterobacter species, Aeromonas hydrophila and Klebsiella species are variable and susceptibility tests should be performed. Proteus species, Serratia species, Morganella species and Pseudomonas aeruginosa are usually resistant.
Anaerobic Bacteria: Bacteroides fragilis and Bacteroides species, Clostridium perfringens, Peptococcus species and Peptostreptococcus species, Fusobacterium necrophorum and Propionibacterium acnes.
Organisms of Sexually Transmitted Diseases: Azithromycin is active against Chlamydia trachomatis and also shows good activity against Treponema pallidum, Neisseria gonorrhoeae, and Haemophilus ducreyi.
Other Organisms: Borrelia burgdorferi (Lyme disease agent), Chlamydia pneumoniae, Mycoplasma pneumoniae, Mycoplasma hominis, Ureaplasma urealyticum, Campylobacter species and Listeria monocytogenes.
Opportunistic Pathogens Associated with HIV Infections: Mycobacterium avium-intracellular complex. Pneumocystis carinii and Toxoplasma gondii.
Inherently resistant organisms: Enterobacteriaceae, Pseudomonas.
Pharmacokinetics: The pharmacokinetic profile of azithromycin is characterized by low plasma concentrations but high and persistent tissue concentrations.
Absorption: Bioavailability after oral administration is approximately 37%. Peak plasma concentrations are attained 2-3 hours after taking the medicinal product.
Distribution: Orally administered azithromycin is widely distributed throughout the body. In pharmacokinetic studies it has been demonstrated that the concentrations of azithromycin measured in tissues are noticeably higher (as much as 50 times) than those measured in plasma, which indicates that the agent strongly binds to tissues. Binding to serum proteins varies according to plasma concentration and ranges from 12% at 0.5 mcg/ml up to 52% at 0.05 mcg azithromycin/ml serum. The mean volume of distribution at steady state (Vss) has been calculated to be 31.1 L/kg.
Elimination: The terminal plasma elimination half-life closely reflects the elimination half-life from tissues of 2-4 days. Approximately 12% of an intravenously administered dose of azithromycin is excreted unchanged in urine within the following three days. Particularly high concentrations of unchanged azithromycin have been found in human bile. Also in bile, ten metabolites were detected, which were formed through N- and O-demethylation, hydroxylation of desosamine and aglycone rings and cleavage of cladinose conjugate. Comparison of the results of liquid chromatography and microbiological analyses has shown that the metabolites of azithromycin are not microbiologically active.
In animal tests, high concentrations of azithromycin have been found in phagocytes. It has also been established that during active phagocytosis, higher concentrations of azithromycin are released from inactive phagocytes. In animal models, this results in high concentrations of azithromycin being delivered to the site of infection.