Pharmacokinetics of difloxacin after intravenous, intramuscular, and intragastric administration to horses.
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.
Fernández-Varón
Emilio
E
Department of Pharmacology, Faculty of Veterinary Medicine, University of Murcia, Campus de Espinardo, 30.071-Murcia, Spain.
Cárceles
Carlos M
CM
Marín
Pedro
P
Martos
Nieves
N
Escudero
Elisa
E
Ayala
Ignacio
I
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
D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D002939:Ciprofloxacin; C047225:difloxacin; D003402:Creatine Kinase