PHARMACOKINETICS OF ENROFLOXACIN AND ITS METABOLITE CIPROFLOXACIN AFTER INTRAVENOUS AND INTRAMUSCULAR ADMINISTRATIONS IN SHEEP

Objective - To evaluate the pharmacokinetics of enrofloxacin and its m etabolite ciprofloxacin after administrations of enrofloxacin in sheep . Design - Crossover study performed by IV and IM 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 t he alternative route. Animals - 6 clinically normal Massese sheep of e ither sex. Procedure - Blood samples were collected at suitable interv als over a 24-hour period, and plasma concentrations of enrofloxacin a nd its main metabolite ciprofloxacin were determined by a high-perform ance liquid chromatography method. Pharmacokinetic variables for both substances after IV and IM enrofloxacin administrations were calculate d by use of statistical moments and were analyzed, using a crossover A NOVA. Results - After IV administration of enrofloxacin, a rapid distr ibution phase was followed by a slower elimination phase. When the sam e dose was administered IM, enrofloxacin was rapidly and almost comple tely absorbed, with bioavailability of 85%. After 24 hours, the mean p lasma concentration of ciprofloxacin was similar to that of the parent drug. Conclusions - The large volume of distribution indicates that e nrofloxacin is widely distributed in the body of sheep. The fraction o f enrofloxacin metabolized to ciprofloxacin (35 and 55% for IV and IM administrations, respectively) suggests that, in this species, the ant imicrobial activity of enrofloxacin could be attributable, at least in part, to its main metabolite ciprofloxacin. Clinical Relevance - IV o r IM administration of 2.5 mg of enrofloxacin/kg provides plasma conce ntrations higher than mean inhibitory concentration for most pathogens in sheep.