Azithro-Natrapharm Mechanism of Action

Pharmacology: Pharmacodynamics: Mechanism of Action: Azithromycin usually is bacteriostatic, although the drug may be bactericidal in high concentrations against selected organisms. Bactericidal activity has been observed in vitro against Streptococcus pyogenes, S. pneumoniae and Haemophilus influenzae. Azithromycin inhibits protein synthesis in susceptible organisms by penetrating the cell wall and binding to 50s ribosomal subunits, thereby inhibiting translocation of aminoacyl transferase-RNA and inhibiting polypeptide synthesis. The site of action of azithromycin appears to be the same as that of the macrolides (ie, erythromycin, clarithromycin), clindamycin, lincomycin and chloramphenicol. The antimicrobial activity of azithromycin is reduced at low pH. Azithromycin concentrates in phagocytes, including polymorphonuclear leukocytes, monocytes, macrophages and fibroblasts. Penetration of the drug into phagocytic cells is necessary for activity against intracellular pathogens (eg, Staphylococcus aureus, Legionella pneumophila, Chlamydia trachomatis, Salmonella typhi).
Spectrum: Azithromycin has an expanded spectrum of activity compared with erythromycin and clarithromycin. Azithromycin is active in vitro against many gram-positive and gram-negative aerobic and anaerobic bacteria as well as Borrelia burgdorferi, Chlamydophila pneumoniae (Chlamydia pneumoniae), C. trachomatis, Mycoplasma pneumoniae and Mycobacterium avium complex (MAC). Azithromycin generally is more active in vitro against gram-negative organisms than erythromycin or clarithromycin and has activity comparable to erythromycin against most gram-positive organisms. Azithromycin has in vitro microbiologic activity similar to clarithromycin or erythromycin against C. pneumoniae and M. pneumoniae, but clarithromycin is 4-fold more active against MAC in vitro than azithromycin. Streptococci and staphylococci that are resistant to erythromycin usually are resistant to azithromycin and clarithromycin. Azithromycin is not inactivated by β-lactamases produced by H. influenzae or Moraxella catarrhalis. Azithromycin appears to have a post-antibiotic inhibitory effect against susceptible gram-positive and gram-negative aerobic organisms. In in vitro studies, exposure of S. pyogenes, S. pneumoniae or H. influenzae for 1-2 hrs to azithromycin concentrations several times higher than the minimum inhibitory concentration (MIC) for the organism resulted in a recovery period of about 3-4, 2.2-5 or 2.5-8 hrs, respectively, after the drug was removed before the organism resumed growth.
Antimicrobial Action: Azithromycin is less active than erythromycin against streptococci and staphylococci, but has greater activity than erythromycin in vitro against some gram-negative organisms eg, H. influenzae and M. catarrhalis (Branhamella catarrhalis), as well as having activity against some of the Enterobacteriaceae eg, Escherichia coli and Salmonella and Shigella spp.
Azithromycin is also more active than erythromycin against C. trachomatis and Ureaplasma urealyticum, and some opportunistic mycobacteria including MAC. It has activity against the protozoa Toxoplasma gondii and Plasmodium falciparum.
Pharmacokinetics: Azithromycin given orally is rapidly absorbed and about 40% bioavailable. Absorption from capsules, but not tablets or suspension, is reduced by food. Peak plasma concentrations (C_max) occur 2-3 hrs after an oral dose and 1-2 hrs after IV dosage. However, azithromycin is extensively distributed into the tissues and tissue concentrations subsequently remain much higher than those in the blood; in contrast to most other antibacterials, plasma concentrations are therefore of little value as a guide to efficacy. High concentrations are taken up into white blood cells. There is little diffusion into the cerebrospinal fluid (CSF) when the meninges are not inflamed. Data from animal studies indicate that azithromycin crosses the placenta. Small amounts of azithromycin are demethylated in the liver and it is excreted in bile mainly as unchanged drug and a number of inactive metabolites have also been detected. About 6% of an oral dose (representing about 20% of the amount in the systemic circulation) is excreted in the urine. The terminal elimination half-life (t_½) is about 68 hrs.