title: Antibiotic transport across bronchial epithelial cells: Effects of molecular weight, LogP and apparent permeability.
abstract: OBJECTIVE
  The first step in developing a new inhalable formulation for the treatment of respiratory diseases is to understand the mechanisms involved in the absorption of drugs after lung deposition. This information could be important for the treatment of bacterial infection in the lung, where low permeability would probably be beneficial, or a systemic infection, where high permeability would be desirable. The goal of this study was to evaluate the transport of several antibiotics (ciprofloxacin, azithromycin, moxifloxacin, rifampicin, doxycycline and tobramycin) across human bronchial airway epithelium and to study the influence of molecular weight and LogP on the apparent permeability.
  
  
  METHODS
  The experiments were conducted using Calu-3 cells seeded in the apical compartment of 24-well Transwell® inserts. The antibiotics transport was measured in both apical to basolateral (A-B) and basolateral to apical (B-A) directions and the apparent permeability of each antibiotic was calculated.
  
  
  RESULTS
  The A-B transport of ciprofloxacin and rifampicin was independent of the initial concentration in the donor compartment, suggesting the involvement of active transporters in their absorption. Moxifloxacin, doxycycline, azithromycin and tobramycin presented a low absorptive permeation in the A-B direction, indicating that these substances could be substrate for efflux pumps. Generally, all antibiotics studied showed low permeabilities in the B-A direction.
  
  
  CONCLUSIONS
  These findings suggest that the inhalation route would be favorable for delivering these specific antibiotics for the treatment of respiratory infection, compared with present oral or intravenous administration.
authors.affiliation: Department of Pharmacy, University of Salerno, Italy; Respiratory Technology, The Woolcock Institute of Medical Research and Discipline of Pharmacology, School of Medicine, The University of Sydney, Sydney, Australia.
authors.forename: Mariateresa
authors.initials: M
authors.lastname: Stigliani
authors.affiliation: Graduate School of Health - Pharmacy, University of Technology, Sydney, Australia; Respiratory Technology, The Woolcock Institute of Medical Research and Discipline of Pharmacology, School of Medicine, The University of Sydney, Sydney, Australia.
authors.forename: Mehra
authors.initials: M
authors.lastname: Haghi
authors.affiliation: Department of Pharmacy, University of Salerno, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Russo
authors.affiliation: Respiratory Technology, The Woolcock Institute of Medical Research and Discipline of Pharmacology, School of Medicine, The University of Sydney, Sydney, Australia.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Young
authors.affiliation: Respiratory Technology, The Woolcock Institute of Medical Research and Discipline of Pharmacology, School of Medicine, The University of Sydney, Sydney, Australia. Electronic address: daniela.traini@sydney.edu.au.
authors.forename: Daniela
authors.initials: D
authors.lastname: Traini
mesh_terms: D020003:1-Octanol / Q000737:chemistry; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D001692:Biological Transport; D001980:Bronchi / Q000166:cytology / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004333:Drug Administration Routes; D004847:Epithelial Cells / Q000378:metabolism*; D006801:Humans; D008970:Molecular Weight; D010539:Permeability; D014867:Water / Q000737:chemistry
chemical_list: D000900:Anti-Bacterial Agents; D014867:Water; D020003:1-Octanol
keywords: Antibiotics; Calu-3; LogP; Lung delivery; Molecular weight; Transport