Pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin after intravenous and intramuscular administrations in sheep.

OBJECTIVE: To evaluate the pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin after administrations of enrofloxacin in sheep.
DESIGN: Crossover study performed by i.v. and i.m. administrations of 2.5 mg of enrofloxacin/kg of body weight to 2 groups of 3 sheep. After a 15-day resting period, the drug administration was repeated, using the alternative route. ANIMALS: 6 clinically normal Massese sheep of either sex. PROCEDURE: Blood samples were collected at suitable intervals over a 24-hour period, and plasma concentrations of enrofloxacin and its main metabolite ciprofloxacin were determined by a high-performance liquid chromatography method. Pharmacokinetic variables for both substances after i.v. and i.m. enrofloxacin administrations were calculated by use of statistical moments and were analyzed, using a crossover ANOVA.
RESULTS: After i.v. administration of enrofloxacin, a rapid distribution phase was followed by a slower elimination phase. When the same dose was administered IM, enrofloxacin was rapidly and almost completely absorbed, with bioavailability of 85%. After 24 hours, the mean plasma concentration of ciprofloxacin was similar to that of the parent drug.
CONCLUSIONS: The large volume of distribution indicates that enrofloxacin is widely distributed in the body of sheep. The fraction of enrofloxacin metabolized to ciprofloxacin (35 and 55% for i.v. and i.m. administrations, respectively) suggests that, in this species, the antimicrobial activity of enrofloxacin could be attributable, at least in part, to its main metabolite ciprofloxacin. CLINICAL RELEVANCE: i.v. or i.m. administration of 2.5 mg of enrofloxacin/kg provides plasma concentrations higher than mean inhibitory concentration for most pathogens in sheep.