title: Efficient drug delivery to alveolar macrophages and lung epithelial lining fluid following pulmonary administration of liposomal ciprofloxacin in rats with pneumonia and estimation of its antibacterial effects.
abstract: The efficacy of pulmonary administration of liposomal ciprofloxacin (CPFX) in pneumonia was evaluated. In brief, the pharmacokinetics following pulmonary administration of liposomal CPFX (particle size, 1,000 nm; dose, 200 microg/kg) were examined in rats with lipopolysaccharide-induced pneumonia as an experimental pneumonia model. Furthermore, the antibacterial effects of liposomal CPFX against the pneumonic causative organisms were estimated by pharmacokinetic/pharmacodynamic (PK/PD) analysis. The time-courses of the concentration of CPFX in alveolar macrophages (AMs) and lung epithelial lining fluid (ELF) following pulmonary administration of liposomal CPFX to rats with pneumonia were markedly higher than that following the administration of free CPFX (200 microg/kg). The time course of the concentrations of CPFX in plasma following pulmonary administration of liposomal CPFX was markedly lower than that in AMs and ELF. These results indicate that pulmonary administration of liposomal CPFX was more effective in delivering CPFX to AMs and ELF compared with free CPFX, and it avoids distribution of CPFX to the blood. According to PK/PD analysis, the liposomal CPFX exhibited potent antibacterial effects against the causative organisms of pneumonia. This study indicates that pulmonary administration of CPFX could be an effective technique for the treatment of pneumonia.
authors.affiliation: Department of Pharmaceutics, Graduate School of Pharmaceutical Sciences, Hokkaido Pharmaceutical University, Katsuraoka-cho, Otaru, Japan. s-chono@hokuyakudai.ac.jp
authors.forename: Sumio
authors.initials: S
authors.lastname: Chono
authors.forename: Tomoharu
authors.initials: T
authors.lastname: Tanino
authors.forename: Toshinobu
authors.initials: T
authors.lastname: Seki
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Morimoto
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage*; D001419:Bacteria / Q000187:drug effects*; D002939:Ciprofloxacin / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000494:pharmacology; D004848:Epithelium / Q000378:metabolism; D008081:Liposomes; D008168:Lung / Q000378:metabolism*; D016676:Macrophages, Alveolar / Q000378:metabolism*; D008297:Male; D018410:Pneumonia, Bacterial / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000890:Anti-Infective Agents; D008081:Liposomes; D002939:Ciprofloxacin