Azito Dry Syrup Mechanism of Action

Pharmacotherapeutic group: Antibacterials for systemic use. ATC code: J01FA10.
Pharmacology: Pharmacodynamics: General properties: Mode of action: AZITO DRY SYRUP is a macrolide antibiotic belonging to the azalide group. The molecule is constructed by adding a nitrogen atom to the lactone ring of erythromycin A. The chemical name of azithromycin is 9-deoxy-9a-aza-9a-methyl-9a-homoerythromycin A. The molecular weight is 749.0. The mechanism of action of azithromycin is based upon the suppression of bacterial protein synthesis by means of binding to the ribosomal 50S sub-unit and inhibition of peptide translocation.
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.
Azithromycin demonstrates cross resistance with erythromycin resistant gram positive isolates.
A decrease in macrolide susceptibility over time has been noted particularly in Streptococcus pneumoniae and Staphylococcus aureus. Similarly, decreased susceptibility has been observed among Streptococcus viridans and Streptococcus agalactiae (Group B) streptococcus against other macrolides and lincosamides.
Breakpoints: Azithromycin susceptibility breakpoints for typical bacterial pathogens published by EUCAST are: See Table 1.

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Susceptibility: The prevalence of acquired resistance may vary geographically and with time for selected species and local information on resistance is desirable, particularly when treating severe infections. As necessary, expert advice should be sought when the local prevalence of resistance is such that the utility of the agent in at least some types of infections is questionable. (See Table 2.)

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Paediatric population: Following the assessment of studies conducted in children, the use of azithromycin is not recommended for the treatment of malaria, neither as monotherapy nor combined with chloroquine or artemisinin based drugs, as non-inferiority to anti-malarial drugs recommended in the treatment of uncomplicated malaria was not established.
Pharmacokinetics: Absorption: Bioavailability after oral administration is approximately 37%. Peak plasma concentrations are attained 2 to 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 microgram/mL up to 52% at 0.05 microgram azithromycin/mL serum. The mean volume of distribution at steady state (VV_ss) 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 to 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.
Toxicology: Preclinical safety data: Phospholipidosis (intracellular phospholipid accumulation) has been observed in several tissues (e.g. eye, dorsal root ganglia, liver, gallbladder, kidney, spleen, and/or pancreas) of mice, rats, and dogs given multiple doses of azithromycin. Phospholipidosis has been observed to a similar extent in the tissues of neonatal rats and dogs. The effect has been shown to be reversible after cessation of azithromycin treatment. The significance of the finding for animals and humans is unknown.
Carcinogenic potential: Long-term studies in animals have not been performed to evaluate carcinogenic potential as the drug is indicated for short-term treatment only and there were no signs indicative of carcinogenic activity.
Mutagenic potential : There was no evidence of a potential for genetic and chromosome mutations in in-vivo and in-vitro test models.
Reproductive toxicity: In animal studies for embryotoxic effects of the substance, no teratogenic effect was observed in mice and rats. In rats, azithromycin doses of 100 and 200 mg/kg bodyweight/day led to mild retardation of foetal ossification and in maternal weight gain. In peri- and postnatal studies in rats, mild retardation following treatment with 50 mg/kg/day azithromycin and above was observed.