Pharmacokinetic and pharmacodynamic efficacy of intrapulmonary administration of ciprofloxacin for the treatment of respiratory infections.
The pharmacokinetic and pharmacodynamic efficacy of intrapulmonary administration of ciprofloxacin (CPFX) for the treatment of respiratory infections caused by pathogenic microorganisms resisting sterilization systems of alveolar macrophages (AMs) was evaluated by comparison with an oral administration. The time-courses of the concentration of CPFX in AMs and lung epithelial lining fluid (ELF) following intrapulmonary administration of CPFX solution to rats (200 microg/kg) were markedly higher than that following oral administration (10 mg/kg). The time-course of the concentrations of CPFX in plasma following intrapulmonary administration was markedly lower than that in AMs and ELF. These results indicate that intrapulmonary administration is more effective in delivering CPFX to AMs and ELF, compared with oral administration, in spite of a low dose and it avoids distribution of CPFX to the blood. In addition, the antibacterial effects of CPFX in AMs and ELF following intrapulmonary administration were evaluated by pharmacokinetics/pharmacodynamics analysis. The concentration of CPFX in AMs and ELF-time curve (AUC)/minimum inhibitory concentration of CPFX (MIC) ratio and the maximum concentration of CPFX in AMs and ELF (Cmax)/MIC ratio were markedly higher than the effective values. The present study indicates that intrapulmonary administration of CPFX is an effective technique for the treatment of respiratory infections.
Chono
Sumio
S
Department of Pharmaceutics, Hokkaido Pharmaceutical University, Japan. s-chono@hokuyakudai.ac.jp
Tanino
Tomoharu
T
Seki
Toshinobu
T
Morimoto
Kazuhiro
K
D000280:Administration, Inhalation; D000284:Administration, Oral; D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000494:pharmacology; D019540:Area Under Curve; D001419:Bacteria / Q000187:drug effects / Q000254:growth & development; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D002939:Ciprofloxacin / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000494:pharmacology; D016676:Macrophages, Alveolar / Q000378:metabolism; D008297:Male; D008826:Microbial Sensitivity Tests; D008954:Models, Biological; D051381:Rats; D017207:Rats, Sprague-Dawley; D012141:Respiratory Tract Infections / Q000188:drug therapy*
D000890:Anti-Infective Agents; D002939:Ciprofloxacin