Azithromycin [HSA-Biotin]

Azithromycin is the first fifteen-membered ring macrolide antibiotic (macrolide) and the first azalide antibiotic (azalide). Its chemical name is 9A-methyl-9-deoxy-9A-aza-9A-same as erythromycin A, which is derived from erythromycin A through chemical modification.

Figure 1. Antibacterial effect of Azithromycin.(Source: Al-Marzooq F,et al., 2023)

Generally speaking, the antibacterial mechanism of azithromycin is roughly the same as that of erythromycin, that is, by reversibly binding to the 50S ribosomal subunit of sensitive microorganisms to prevent the translation and assembly of nascent peptide chains, ultimately inhibiting the translation of bacterial proteins that rely on the central dogma of the cell. process to inhibit bacterial growth and achieve antibacterial effects. However, azithromycin is more acid stable than erythromycin and is more easily absorbed through the gastrointestinal tract. At the same time, azithromycin has a more even distribution in cell tissues and has a long-lasting high tissue concentration. The half-life can be as long as 40 hours, so the antibacterial time is longer than that of erythromycin. Azithromycin has significant anti-inflammatory activity. Studies have shown that azithromycin can reduce the levels of a variety of inflammatory cytokines, including interleukin (IL)-1β, IL-2, tumor necrosis factor (TNF), and granulocyte-macrophage colony-stimulating factor (GM-CSF). Azithromycin is also thought to inhibit IL-6 and IL-12 and promote IL-10 production by activated mouse macrophages. There is evidence that these anti-inflammatory effects are achieved by inhibiting the activation of nuclear factor-κB (NF-κB). In addition, azithromycin can also inhibit the activation of the transcription factor activator protein-1 (AP-1), which can regulate the expression of pro-inflammatory cytokines such as IL-8, IL-6, TNF-α, and IL-1β. Therefore, azithromycin's reduction in IL-8 production may also be through its inhibition of mitogen-activated protein kinase and extracellular-regulated kinase.
The anti-inflammatory effect of azithromycin is mainly manifested in immune cells and epithelial cells. Some studies have found that azithromycin has stimulatory effects on immune cells and epithelial cells and modulates extracellular signal-regulated kinase 1/2 (ERK1/2) signaling by stimulating oxidative burst associated with neutrophil degranulation and phagocytosis. After these initial stimulations, AP-1, NF-κB, inflammatory cytokines, and mucins are released, thereby exerting the overall anti-inflammatory effects of azithromycin. In macrophages, azithromycin reduces lipopolysaccharide-induced pro-inflammatory cytokines, increases phagocytosis, and achieves enhanced lysosome promote to oxidative stress and macrophage M2 polarization by inhibiting the AP-1 target. Azithromycin also inhibits T cells by inhibiting the calcineurin signaling pathway, mammalian target of rapamycin activity, and NF-κB activation. In addition, in an in vitro respiratory epithelial cell model, azithromycin can reduce mucus production and enhance epithelial barrier thickness. It can also reduce matrix metalloproteinase (MMP) activity after bacterial lipopolysaccharide attack, thereby reducing inflammatory signaling, which helps maintain cell health, integrity and functionality of the epithelial barrier. Studies have confirmed that azithromycin can improve sulfur dioxide-induced airway epithelial damage and inflammatory response. Azithromycin has a variety of immunomodulatory effects, and its immunomodulatory effects are closely related to its anti-inflammatory effects. In the mouse experimental model of Pseudomonas aeruginosa lung infection and lipopolysaccharide-induced inflammation, azithromycin can significantly reduce the levels of macrophage inflammatory factors, myeloperoxidase, TNF-α and IL-1β, thereby changing the macrophage activity. Azithromycin has antiviral properties and works synergistically with other antiviral medications. The antiviral activity of azithromycin has been confirmed by clinical use of a large number of viruses and scientific experiments, including respiratory syncytial virus, Ebola virus, Zika virus, H1N1 influenza virus, enterovirus and rhinovirus. in vitro antiviral activity studies show that, except for H1N1 influenza virus, the 50% inhibitory concentration range of azithromycin for the above viruses is 1 to 6 μmol/L. In a 2177 drug screening experiment for the treatment of Zika virus, azithromycin was confirmed to reduce virus proliferation and virus-induced cytopathic effects in glial cell lines and human astrocytes.

Azithromycin can be quickly absorbed by the human body after oral administration, and can quickly enter the intercellular space from the blood to exert its therapeutic effect. Pharmacological studies have found that the bioavailability of azithromycin reaches 37%. Azithromycin can reach peak plasma concentration 2.5 to 2.6 hours after oral administration, and the peak plasma concentration reaches 0.4 to 0.45 mg/L. Azithromycin is widely distributed in the human body, and its blood concentration in various tissues is 10 to 100 times higher than that of the same period, which shows that the drug can effectively combine with tissue mass. In addition, azithromycin can accumulate in macrophages or polychromatic leukocytes after administration, resulting in azithromycin having a wider distribution volume and wider cell permeability than similar antibiotics, making it easier to administer orally. In addition, because azithromycin has a long residence time in human tissues and is released slowly, patients can still detect the original form of the drug two weeks after taking a single dose. Studies have found that the urinary excretion rate of azithromycin within 7 days of medication is less than 6%, and the renal clearance rate is 1.67-3.156ml/s. It can be seen that as long as a sufficient amount of azithromycin is administered, it usually only needs to be administered once a day to have its effect, and the drug can maintain its effective concentration for a longer period of time.

Azithrocin