Pharmacology: Pharmacodynamics: Azithromycin 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 mechanism of action of azithromycin is based upon the suppression of bacterial protein synthesis by binding to the ribosomal 50s sub-unit and inhibition of peptide translocation.
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.
Pharmacokinetics: Absorption: Following oral administration in humans, azithromycin is widely distributed throughout the body; bioavailability is approximately 37%. The time taken to peak plasma levels is 2-3 hours.
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. The mean volume of distribution at the steady state (VVss) has been calculated to be 31.1 l/kg.
Elimination: Plasma terminal elimination half-life closely reflects the tissue depletion half-life of 2 to 4 days. Approximately 12% of an intravenously administered dose is excreted in the urine within the following three days as the parent drug. Particularly high concentrations of unchanged drug have been found in human bile, together with 10 metabolites, formed by N- and O-demethylation, by hydroxylation of the desosamine and aglycone rings, and by cleavage of the cladinose conjugate. Comparison of liquid chromatography and microbiological analyses in tissues suggests that metabolites play no part in the microbiological activity of azithromycin.