Aerosol-Based Efficient Delivery of Clarithromycin, a Macrolide Antimicrobial Agent, to Lung Epithelial Lining Fluid and Alveolar Macrophages for Treatment of Respiratory Infections

作者：Togami Kohei; Chono Sumio^*; Morimoto Kazuhiro

来源：Journal of Aerosol Medicine and Pulmonary Drug Delivery, 2012, 25(2): 110-115.

DOI：10.1089/jamp.2011.0894

• aerosol-based pulmonary drug delivery system
• clarithromycin
• macrolides
• lung epithelial lining fluid and alveolar macrophages
• respiratory infections
• PK/PD

Background: Macrolide antimicrobial agents are generally given by the oral route for the treatment of respiratory infections caused by pathogenic microorganisms infected in lung epithelial lining fluid (ELF) and alveolar macrophages (AMs). However, because macrolides distribute to many different tissues via the blood after oral administration, systemic side effects are frequently induced. In contrast with oral administration, aerosolization may be an efficient method for delivering macrolides directly to ELF and AMs. In this study, the efficacy of aerosol-based delivery of clarithromycin (CAM), as a model macrolide, for the treatment of respiratory infections was evaluated by comparison with oral administration.
Method: The aerosol formulation of CAM (0.2 mg/kg) was administered to rat lungs using a Liquid MicroSprayer (R). The oral formulation of CAM (50 mg/kg) was used for comparison. Time courses of concentrations of CAM in ELF and AMs following administration were obtained, and then the bioavailability (BA) was calculated. In addition, the area under the concentrations of CAM in ELF and AMs-time curve/minimum inhibitory concentration at which 90% of isolates ratio [area under the curve (AUC/MIC90)] were calculated to estimate the antibacterial effects in ELF and AMs.
Results: The BA of CAM in ELF and AMs following administration of aerosol formulation were markedly greater than that following administration of oral formulation. This indicates that the aerosol formulation is more effective in delivering CAM to ELF and AMs, compared with the oral formulation, despite a low dose. The AUC/MIC90 of CAM in ELF and AMs were 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 ELF and AMs.
Conclusions: This study suggests that aerosol formulation of macrolides is an effective pulmonary drug delivery system for the treatment of respiratory infections.

• 出版日期2012-4