Aerosol-based efficient delivery of telithromycin, a ketolide antimicrobial agent, to lung epithelial lining fluid and alveolar macrophages for treatment of respiratory infections.
OBJECTIVE
The efficacy of aerosol-based delivery of telithromycin (TEL), as a model antimicrobial agent, for the treatment of respiratory infections was evaluated by comparison with oral administration.


METHODS
The aerosol formulation (0.2 mg/kg) was administered to rat lungs using a Liquid MicroSprayer.


CONCLUSIONS
The time courses of the concentration of TEL in lung epithelial lining fluid (ELF) and alveolar macrophages (AMs) following administration of an aerosol formulation to rat lungs were markedly higher than that following the administration of an oral formulation (50 mg/kg). The time course of the concentrations of TEL in plasma following administration of the aerosol formulation was markedly lower than that in ELF and AMs. These results indicate that the aerosol formulation is more effective in delivering TEL to ELF and AMs, compared to the oral formulation, despite a low dose and it avoids distribution of TEL to the blood. In addition, the antibacterial effects of TEL in ELF and AMs following administration of the aerosol formulation were estimated by pharmacokinetics/pharmacodynamics analysis. The concentrations of TEL in ELF and the AMs time curve/minimum inhibitory concentration of TEL ratio were markedly higher than the effective values.


CONCLUSIONS
This study indicates that an antibiotic aerosol formulation may be an effective pulmonary drug delivery system for the treatment of respiratory infections.
Department of Pharmaceutics, Graduate School of Pharmaceutical Sciences, Hokkaido Pharmaceutical University, Otaru, Japan.
Kohei
K
Togami
Sumio
S
Chono
Toshinobu
T
Seki
Kazuhiro
K
Morimoto
D000280:Administration, Inhalation; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D004847:Epithelial Cells / Q000378:metabolism; D045604:Extracellular Fluid / Q000378:metabolism*; D006193:Haemophilus influenzae / Q000187:drug effects; D048628:Ketolides / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D008168:Lung / Q000378:metabolism*; D016676:Macrophages, Alveolar / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012141:Respiratory Tract Infections / Q000188:drug therapy; D013296:Streptococcus pneumoniae / Q000187:drug effects; D013678:Technology, Pharmaceutical
D000900:Anti-Bacterial Agents; D048628:Ketolides; C106791:telithromycin