Azipro Mechanism of Action

Pharmacotherapeutic group: Antibacterials for systemic use; Macrolides.
Pharmacology: Azithromycin is an azalide, a sub-class of the macrolide antibiotics. By binding to the 50S-ribosomal sub-unit, azithromycin avoids the translocation of peptide chains from one side of the ribosome to the other. As a consequence of this, RNA-dependent protein synthesis in sensitive organisms is prevented.
PK/PD relationship: For azithromycin the AUC/MIC is the major PK/PD parameter correlating best with the efficacy of azithromycin.
Mechanism of resistance: Resistance to azithromycin may be inherent or acquired. There are three main mechanisms of resistance in bacteria: target site alteration, alteration in antibiotic transport and modification of the antibiotic.
Complete cross resistance exists among Streptococcus pneumoniae, beta-haemolytic streptococcus of group A, Enterococcus faecalis and Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA) to erythromycin, azithromycin, other macrolides and lincosamides.
Pharmaokinetics: Absorption: After oral administration the bioavailability of azithromycin is approximately 37%. Peak plasma levels are reached after 2-3 hours (Cmax after a single dose of 500 mg orally was approximately 0.4 mg/L).
Distribution: Concentrations in target tissues such as lung, tonsil, and prostate exceed the MIC90 for likely pathogens after a single dose of 500 mg. In serum the protein binding of azithromycin is variable and depending on the serum concentration varies from 50% in 0.05 mg/L to 12% in 0.5 mg/L.
Excretion: Plasma terminal elimination half-life closely reflects the tissue depletion half-life of 2 to 4 days. Biliary excretion of azithromycin, predominantly in unchanged form, is a major route of elimination.
Following oral administration, Azithromycin is rapidly absorbed and widely distributed throughout the body. Rapid distribution into tissues and high concentration within cells result, it significantly higher Azithromycin concentrations in tissues than in plasma of serum.
Biliary excretion of Azithromycin, predominantly as unchanged drug, is a major route of elimination. Over the course of a week, approximately 6% of the administered dose appeared as unchanged drug in urine. Azithromycin concentrates in phagocytes and fibroblasts; concentration in phagocytes may contribute to drug distribution in inflamed tissue.