title: Inhalation of macrolides: a novel approach to treatment of pulmonary infections.
abstract: Systemic antibiotic treatment is established for many pulmonary diseases, e.g., cystic fibrosis (CF), bronchiectasis and chronic obstructive pulmonary disease (COPD) where recurrent bacterial infections cause a progressive decline in lung function. In the last decades inhalative administration of antibiotics was introduced into clinical routine, especially tobramycin, colistin, and aztreonam for treatment of CF and bronchiectasis. Even though they are important in systemic treatment of these diseases due to their antimicrobial spectrum and anti-inflammatory and immunomodulatory properties, macrolides (e.g., azithromycin, clarithromycin, erythromycin, and telithromycin) up to now are not administered by inhalation. The number of in vitro aerosol studies and in vivo inhalation studies is also sparse. We analyzed publications on preparation and administration of macrolide aerosols available in PUBMED focusing on recent publications. Studies with solutions and dry powder aerosols were published. Publications investigating physicochemical properties of aerosols demonstrated that macrolide aerosols may serve for inhalation and will achieve sufficient lung deposition and that the bitter taste can be masked. In vivo studies in rats demonstrated high concentrations and areas under the curve sufficient for antimicrobial treatment in alveolar macrophages and epithelial lining fluid without lung toxicity. The obtained data demonstrate the feasibility of macrolide inhalation which should be further investigated.
authors.affiliation: Drug Regulatory Affairs, Pharmaceutical Institute, University Bonn, Bonn, Germany, Ruediger.Siekmeier@bfarm.de.
authors.forename: R
authors.initials: R
authors.lastname: Siekmeier
authors.forename: T
authors.initials: T
authors.lastname: Hofmann
authors.forename: G
authors.initials: G
authors.lastname: Scheuch
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D017963:Azithromycin / Q000627:therapeutic use; D001987:Bronchiectasis / Q000188:drug therapy* / Q000382:microbiology / Q000503:physiopathology; D017291:Clarithromycin / Q000627:therapeutic use; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000382:microbiology / Q000503:physiopathology; D004917:Erythromycin / Q000627:therapeutic use; D006801:Humans; D048628:Ketolides / Q000627:therapeutic use; D008168:Lung / Q000187:drug effects* / Q000382:microbiology / Q000503:physiopathology; D018942:Macrolides / Q000627:therapeutic use*; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000382:microbiology / Q000503:physiopathology; D051381:Rats
chemical_list: D000336:Aerosols; D000900:Anti-Bacterial Agents; D048628:Ketolides; D018942:Macrolides; D004917:Erythromycin; D017963:Azithromycin; D017291:Clarithromycin; C106791:telithromycin