title: Pulmonary pharmacokinetics of desfuroylceftiofur acetamide after nebulisation or intramuscular administration of ceftiofur sodium to weanling foals.
abstract: BACKGROUND
  Administration of ceftiofur sodium via nebulisation has been recommended for the treatment of bronchopneumonia in horses, despite the lack of pharmacokinetic and safety data.
  
  
  OBJECTIVE
  To compare concentrations of desfuroylceftiofur acetamide (DCA) in plasma and pulmonary epithelial lining fluid (PELF) of foals after nebulisation or i.m. administration of ceftiofur sodium and to determine if nebulisation of ceftiofur sodium induces airway inflammation.
  
  
  METHODS
  Randomised experimental study.
  
  
  METHODS
  Six weanling foals received ceftiofur sodium (2.2 mg/kg bwt daily for 5 doses) by the i.m. route and 6 foals received the same dose by nebulisation. Concentrations of DCA in plasma and PELF were measured after Doses 1 and 5, and differential cell counts were performed on bronchoalveolar lavage samples obtained after Dose 5.
  
  
  RESULTS
  Foals receiving ceftiofur sodium via nebulisation had significantly lower peak concentrations (0.15 ± 0.12 vs. 6.15 ± 0.75 mg/l) and area under the curve (1.26 ± 0.96 vs. 37.63 ± 4.01 mg●h/l) in plasma compared with those receiving the drug by the i.m. route. In contrast, foals receiving ceftiofur sodium via nebulisation had significantly higher peak concentrations (4.52 ± 2.91 vs. 0.73 ± 0.73 mg/l) and area under the curve (24.14 ± 14.09 vs. 5.91 ± 3.28 mg●h/l) in PELF compared with those receiving the drug by the i.m. route. Cell concentration and differential cell count in bronchoalveolar lavage fluid of foals nebulised with ceftiofur sodium were not significantly different from those of foals nebulised with saline.
  
  
  CONCLUSIONS
  Administration of ceftiofur sodium via nebulisation is well tolerated and DCA concentrations in PELF remain above the minimum inhibitory concentration of the drug required to inhibit the growth of 90% of Streptococcus zooepidemicus for approximately 24 h after administration. Nebulised ceftiofur sodium warrants further investigation for the treatment of bacterial infections of the lower respiratory tract in horses.
authors: Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, USA.
authors: L
authors: L
authors: Fultz
authors: Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, USA.
authors: S
authors: S
authors: Giguère
authors: Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, USA.
authors: L J
authors: LJ
authors: Berghaus
authors: Metabolism and Safety, Zoetis, Kalamazoo, Michigan, USA.
authors: G S
authors: GS
authors: Grover
authors: Metabolism and Safety, Zoetis, Kalamazoo, Michigan, USA.
authors: D A
authors: DA
authors: Merritt
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D001826:Body Fluids; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002511:Cephalosporins / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D006736:Horses / Q000378:metabolism*; D007273:Injections, Intramuscular; D008168:Lung / Q000378:metabolism*
chemical_list: D000336:Aerosols; D002511:Cephalosporins; C063324:desfuroylceftiofur; C053503:ceftiofur
keywords: aerosol; ceftiofur sodium; foal; horse; nebulisation; pneumonia