Pharmacokinetics after intravenous and oral administration of enrofloxacin in sheep

Objective-To compare pharmacokinetics of enrofloxacin administered IV and in various oral preparations to ewes. Animals-5 mature Katahdin ewes weighing 42 to 50 kg. Procedure-Ewes received 4 single-dose treatments of enrofloxacin in a nonrandomized crossover design followed by a multiple-dose oral regimen. Single-dose treatments consisted of an IV bolus of enrofloxacin (5 mg/kg), an oral drench (10 mg/kg) made from crushed enrofloxacin tablets, oral administration in feed (10 mg/kg- mixture of crushed enrofloxacin tablets and grain), and another type of oral administration in feed (10 mg/kg, mixture of enrofloxacin solution and grain). The multiple-dose regimen consisted of feeding a mixture of enrofloxacin solution and grain (10 mg/kg, q 24 h, for 7 days). Plasma concentrations of enrofloxacin and ciprofloxacin were measured by use of high-performance liquid chromatography. Results-Harmonic mean half-life for oral administration was 14.80, 10.80, and 13.07 hours, respectively, for the oral drench, crushed tablets in grain, and enrofloxacin solution in grain. Oral bioavailability for the oral drench, crushed tablets in grain, and enrofloxacin in grain was 4789, 98.07, and 94.60%, respectively, and median maximum concentration (C-max) was 1.61, 2.69, and 2.26 mug/ml, respectively. Median C-max of the multiple-dose regimen was 2.99 mug/ml. Conclusions and Clinical Relevance-Enrofloxacin administered orally to sheep has a prolonged half-life and high oral bioavailability. Oral administration at 10 mg/kg, q 24 h, was sufficient to achieve a plasma concentration of 8 to 10 times the minimum inhibitory concentration (MIC) of any microorganism with an MIC less than or equal to 0.29 mug/ml.