Single-dose azithromycin for acute otitis media: A pharmacokinetic/pharmacodynamic rationale

Abstract 

The pharmacokinetic (PK) and pharmacodynamic (PD) properties of the azalide azithromycin distinguish it from other antibiotics. The PK profile of azithromycin features high tissue-to-serum ratios, including high concentrations in the middle ear, and a prolonged elimination half-life. These characteristics result from the accumulation of drug within cells and its subsequent slow, sustained release from cells and tissues into the bloodstream. The PD properties of azithromycin include bactericidal activity against key respiratory tract pathogens and a prolonged postantibiotic, or persistent, effect. In addition, white blood cells deliver the drug to infected foci, thereby enhancing local tissue concentrations and improving in vivo efficacy. Recent PK studies in mice suggest that a single, large dose of azithromycin achieves higher tissue concentrations than do multidose regimens. Other studies in animal infection models, in particular, a gerbil model of acute otitis media, have demonstrated improved bacterial eradication when azithromycin is administered as a single dose rather than divided over 2 or 3 days. Taken together, the results from these preclinical studies provide a PK/PD rationale for the use of single-dose azithromycin in the treatment of acute otitis media. Clinical data on the efficacy and safety of single-dose azithromycin for the treatment of acute otitis media in children are presented in 2 accompanying articles in this supplement.

Keywords:  azithromycin, acute otitis media, pharmacokinetics, pharmacodynamics

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