title: Pharmacokinetics of difloxacin after intravenous, intramuscular, and intragastric administration to horses.
abstract: OBJECTIVE
  To study the pharmacokinetics of difloxacin (5 mg/kg) following IV, IM, and intragastric (IG) administration to healthy horses.
  
  
  METHODS
  6 healthy mature horses.
  
  
  METHODS
  A crossover study design with 3 phases was used (15-day washout periods between treatments). An injectable formulation of difloxacin (5%) was administered IV and IM in single doses (5 mg/kg); for IG administration, an oral solution was prepared and administered via nasogastric tube. Blood samples were collected before and at intervals after each administration. A high-performance liquid chromatography assay with fluorescence detection was used to determine plasma difloxacin concentrations. Pharmacokinetic parameters of difloxacin were analyzed. Plasma creatine kinase activity was monitored to assess tissue damage.
  
  
  RESULTS
  Difloxacin plasma concentration versus time data after IV administration were best described by a 2-compartment open model. The disposition of difloxacin following IM or IG administration was best described by a 1-compartment model. Mean half-life for difloxacin administered IV, IM, and IG was 2.66, 5.72, and 10.75 hours, respectively. Clearance after IV administration was 0.28 L/kg.h. After IM administration, the absolute mean +/- SD bioavailability was 95.81 +/- 3.11% and maximum plasma concentration (Cmax) was 1.48 +/- 0.12 mg/L. After IG administration, the absolute bioavailability was 68.62 +/- 10.60% and Cmax was 0.732 +/- 0.05 mg/L. At 12 hours after IM administration, plasma creatine kinase activity had increased 7-fold, compared with the preinjection value.
  
  
  CONCLUSIONS
  Data suggest that difloxacin is likely to be effective for treating susceptible bacterial infections in horses.
authors.affiliation: Department of Pharmacology, Faculty of Veterinary Medicine, University of Murcia, Campus de Espinardo, 30.071-Murcia, Spain.
authors.forename: Emilio
authors.initials: E
authors.lastname: Fernández-Varón
authors.forename: Carlos M
authors.initials: CM
authors.lastname: Cárceles
authors.forename: Pedro
authors.initials: P
authors.lastname: Marín
authors.forename: Nieves
authors.initials: N
authors.lastname: Martos
authors.forename: Elisa
authors.initials: E
authors.lastname: Escudero
authors.forename: Ignacio
authors.initials: I
authors.lastname: Ayala
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002939:Ciprofloxacin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D003402:Creatine Kinase / Q000097:blood; D018592:Cross-Over Studies; D024841:Fluoroquinolones / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D006207:Half-Life; D006736:Horses / Q000378:metabolism*; D007273:Injections, Intramuscular; D007275:Injections, Intravenous
chemical_list: D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D002939:Ciprofloxacin; C047225:difloxacin; D003402:Creatine Kinase