title: Aerosol Route to Administer Teicoplanin in Mechanical Ventilation: In Vitro Study, Lung Deposition and Pharmacokinetic Analyses in Pigs.
abstract: BACKGROUND
  Glycopeptides given intravenously achieve low airway concentrations. Nebulization of teicoplanin may be an efficient way of delivering a high concentration of this antibiotic to the lung. This multistep study assessed the feasibility of teicoplanin nebulization during mechanical ventilation by evaluating: the stability of its antibiotic effect; epithelial tolerance; lung deposition and systemic absorption in ventilated pigs.
  
  
  METHODS
  Nebulized and non-nebulized teicoplanin activity was tested on Staphylococcus aureus cultures. The cytotoxic effect of teicoplanin on human respiratory epithelial cells was assessed by measuring lactate dehydrogenase activity released, cell viability, and transepithelial electrical resistance. Volume median diameter of particles of nebulized teicoplanin was measured by laser diffraction during mechanical ventilation. The deposited mass of teicoplanin nebulized with a vibrating mesh nebulizer in ventilated piglets was assessed by scintigraphy. Blood pharmacokinetics of teicoplanin administered either intravenously or by nebulization was compared.
  
  
  RESULTS
  No decrease of antibiotic activity was observed after nebulization. In vitro cytotoxicity of teicoplanin was only observed with 1000 times the dose recommended for intravenous administration. Volume median diameter of particles was 2.5±0.1 μm. Of the initial nebulizer charge of teicoplanin, 24±7% was present in the lungs of ventilated pigs after the nebulization. Amount absorbed in blood was low (3.4%±0.9%) after nebulization, and blood stream elimination half-life value was 25.4 h.
  
  
  CONCLUSIONS
  Teicoplanin was administered efficiently by nebulization during mechanical ventilation, without any effect on its pharmacological properties or any cytotoxicity. The pharmacokinetic parameters are promising in view of its time-dependent killing process. All the results of our multi-step study highlighted the potential of teicoplanin to be nebulized during mechanical ventilation.
authors.affiliation: 1 Université François Rabelais de Tours , EA6305, Tours, France .|2 INSERM, U1100, Centre d'Etude des Pathologies Respiratoires , Tours, France .|3 CHRU de Tours, Service de Réanimation Polyvalente , Tours, France .
authors.forename: Antoine
authors.initials: A
authors.lastname: Guillon
authors.affiliation: 1 Université François Rabelais de Tours , EA6305, Tours, France .|2 INSERM, U1100, Centre d'Etude des Pathologies Respiratoires , Tours, France .|3 CHRU de Tours, Service de Réanimation Polyvalente , Tours, France .
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Mercier
authors.affiliation: 4 Université François Rabelais de Tours , UMR1282 ISP, Tours, France .|5 INRA , UMR 1282 ISP, Nouzilly, France .|6 Service de Bactériologie-Virologie , Tours, France .
authors.forename: Philippe
authors.initials: P
authors.lastname: Lanotte
authors.affiliation: 4 Université François Rabelais de Tours , UMR1282 ISP, Tours, France .|6 Service de Bactériologie-Virologie , Tours, France .
authors.forename: Eve
authors.initials: E
authors.lastname: Haguenoer
authors.affiliation: 7 Laboratoire de Pharmacologie-Toxicologie , Tours, France .
authors.forename: François
authors.initials: F
authors.lastname: Darrouzain
authors.affiliation: 8 INRA , UE1277, Plate-Forme d'Infectiologie Expérimentale, Nouzilly, France .
authors.forename: Céline
authors.initials: C
authors.lastname: Barc
authors.affiliation: 8 INRA , UE1277, Plate-Forme d'Infectiologie Expérimentale, Nouzilly, France .
authors.forename: Pierre
authors.initials: P
authors.lastname: Sarradin
authors.affiliation: 1 Université François Rabelais de Tours , EA6305, Tours, France .|2 INSERM, U1100, Centre d'Etude des Pathologies Respiratoires , Tours, France .
authors.forename: Mustapha
authors.initials: M
authors.lastname: Si-Tahar
authors.affiliation: 1 Université François Rabelais de Tours , EA6305, Tours, France .|2 INSERM, U1100, Centre d'Etude des Pathologies Respiratoires , Tours, France .
authors.forename: Nathalie
authors.initials: N
authors.lastname: Heuzé-Vourc'h
authors.affiliation: 1 Université François Rabelais de Tours , EA6305, Tours, France .|2 INSERM, U1100, Centre d'Etude des Pathologies Respiratoires , Tours, France .
authors.forename: Patrice
authors.initials: P
authors.lastname: Diot
authors.affiliation: 1 Université François Rabelais de Tours , EA6305, Tours, France .|9 Aerodrug, Université François Rabelais , Faculté de Médecine, Tours, France .
authors.forename: Laurent
authors.initials: L
authors.lastname: Vecellio
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics* / Q000633:toxicity; D002460:Cell Line; D004355:Drug Stability; D004867:Equipment Design; D005240:Feasibility Studies; D006207:Half-Life; D007275:Injections, Intravenous; D008168:Lung / Q000033:anatomy & histology / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D008953:Models, Anatomic; D023421:Models, Animal; D009330:Nebulizers and Vaporizers; D010316:Particle Size; D011877:Radionuclide Imaging; D012121:Respiration, Artificial / Q000295:instrumentation*; D013211:Staphylococcus aureus / Q000187:drug effects / Q000254:growth & development; D013552:Swine; D017334:Teicoplanin / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics* / Q000633:toxicity
chemical_list: D000336:Aerosols; D000900:Anti-Bacterial Agents; D017334:Teicoplanin
keywords: aerosol; glycopeptide; pharmacokinetics; ventilator-associated pneumonia