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.