Aerosol-based efficient delivery of azithromycin to alveolar macrophages for treatment of respiratory infections.
The efficacy of aerosol-based delivery of azithromycin (AZM) for the treatment of respiratory infections caused by pathogenic microorganisms infected in alveolar macrophages (AMs) was evaluated by comparison with oral administration. The aerosol formulation of AZM (0.2 mg/kg) was administered to rat lungs using a Liquid MicroSprayer(®). The oral formulation of AZM (50 mg/kg) was used for comparison. Time-courses of concentrations of AZM in AMs following administration were obtained, and then the therapeutic availability (TA) was calculated. In addition, the area under the concentrations of AZM in AMs - time curve/minimum inhibitory concentration at which 90% of isolates ratio (AUC/MIC90) were calculated to estimate the antibacterial effects in AMs. The TA of AZM in AMs following administration of aerosol formulation was markedly greater than that following administration of oral formulation. In addition, the AUC/MIC90 of AZM in AMs was markedly higher than the effective values. This indicates that the aerosol formulation could be useful for the treatment of respiratory infections caused by pathogenic microorganisms infected in AMs. This study suggests that aerosolized AZM is an effective pulmonary drug delivery system for the treatment of respiratory infections.
Department of Pharmaceutics, Graduate School of Pharmaceutical Sciences, Hokkaido Pharmaceutical University, Otaru-city, Japan.
Kohei
K
Togami
Sumio
S
Chono
Kazuhiro
K
Morimoto
D000280:Administration, Inhalation; D000284:Administration, Oral; D000336:Aerosols / Q000008:administration & dosage / Q000493:pharmacokinetics; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D019540:Area Under Curve; D017963:Azithromycin / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D002626:Chemistry, Pharmaceutical / Q000379:methods; D016503:Drug Delivery Systems / Q000379:methods; D008168:Lung / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012141:Respiratory Tract Infections / Q000188:drug therapy* / Q000378:metabolism
D000336:Aerosols; D000900:Anti-Bacterial Agents; D017963:Azithromycin