title: Plasma and pulmonary pharmacokinetics of desfuroylceftiofur acetamide after weekly administration of ceftiofur crystalline free acid to adult horses.
abstract: BACKGROUND
  Current labelling for the use of ceftiofur crystalline free acid (CCFA) in horses states that 2 i.m. doses must be administered 4 days apart to provide 10 days of therapeutic coverage. A 10 day treatment regimen is not sufficient for the long-term treatment of horses with severe lung consolidation or pleuropneumonia. There are currently no data to guide an appropriate dosing interval when a longer treatment regimen is warranted.
  
  
  OBJECTIVE
  To determine steady-state plasma and pulmonary epithelial lining fluid (PELF) concentrations of desfuroylceftiofur acetamide (DCA) after weekly i.m. administration of CCFA to adult horses.
  
  
  METHODS
  Experimental study.
  
  
  METHODS
  Seven adult horses received i.m. CCFA at a dose of 6.6 mg/kg bwt on Day 0, Day 4 and every 7 days thereafter for 3 additional doses. Concentrations of DCA in plasma and PELF were measured at various time intervals.
  
  
  RESULTS
  After weekly i.m. administration, the mean (± s.d.) steady-state peak DCA concentration in plasma (2.87 ± 1.50 μg/ml) was significantly higher than that in PELF (0.84 ± 0.53 μg/ml). Mean terminal half-lives in plasma (77.5 ± 17.5 h) and PELF (92.8 ± 59.0 h) were not significantly different. Concentrations of DCA in plasma and PELF remained in the therapeutic range for the entire dosing interval.
  
  
  CONCLUSIONS
  After the initial 2-dose regimen 4 days apart, weekly i.m. administration of CCFA was well tolerated and resulted in plasma and PELF DCA concentrations above the minimal inhibitory concentration that inhibits growth of at least 90% of common lower respiratory tract pathogens of horses.
  
  
  CONCLUSIONS
  Weekly administration of CCFA would appear appropriate when a treatment regimen longer than 10 days is warranted based on clinical signs and disease severity.
authors.affiliation: Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, USA.
authors.forename: L
authors.initials: L
authors.lastname: Fultz
authors.forename: S
authors.initials: S
authors.lastname: Giguère
authors.forename: L J
authors.initials: LJ
authors.lastname: Berghaus
authors.forename: J L
authors.initials: JL
authors.lastname: Davis
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics; D019540:Area Under Curve; D002511:Cephalosporins / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D004334:Drug Administration Schedule; D005260:Female; D006207:Half-Life; D006736:Horses / Q000097:blood / Q000378:metabolism*; D008168:Lung / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; C063324:desfuroylceftiofur; C053503:ceftiofur
keywords: Excede; ceftiofur; cephalosporin; horse