PHARMACOKINETICS OF ENROFLOXACIN IN ADULT HORSES AND CONCENTRATION OFTHE DRUG IN SERUM, BODY-FLUIDS, AND ENDOMETRIAL TISSUES AFTER REPEATED INTRAGASTRICALLY ADMINISTERED DOSES

Objective-To investigate the pharmacokinetics of enrofloxacin in adult horses.Design-2-dose oral and IV cross-over trial followed by multipl e oral doses. Animals-8 clinically normal adult horses. Procedure-Enro floxacin was administered at dosages of 2.5 mg/kg of body weight to 4 horses and 5.0 mg/kg to 4 other horses. Each dose was given by the int ragastric and IV routes, using a cross-over design. After the first in tragastric dose, 5 additional doses were administered at 12-hour inter vals. Enrofloxacin concentrations were measured in serum, synovial flu id, peritoneal fluid, urine, CSF, and endometrial tissues. Results-Dis position of enrofloxacin after IV administration conformed to a 2-comp artment model with an elimination half-life of 5.95 and 6.09 hours for the low and high dose, respectively. After the first intragastric adm inistration, time to peak concentration was 1.0 +/- 0.35 and 1.25 +/- 0.43 hours, and the bioavailability was 57.39 +/- 8.45 and 62.52 +/- 1 9.65% for the low and high dose, respectively. After multiple intragas tric administration, peak serum concentration (at 72 to 96 hours) was 2.62 +/- 0.61 mu g/ml for the low dose and 5.97 +/- 1.56 mu g/ml for t he high dose. After multiple intragastric doses, synovial fluid, urine , and endometrial tissue concentrations exceeded serum concentrations. Peritoneal fluid and CSF concentrations were lower than serum concent rations. Conclusions-Computer modeling of the pharmacokinetic variable s suggested that a single daily IV administered dose of 5.5 mg/kg, or orally administered doses of 7.5 mg/kg every 24 hours or 4.0 mg/kg eve ry 12 hours, would be effective in horses. Additional studies are nece ssary to confirm the efficacy and safety of these dosages in a clinica l setting.