Pharmacokinetic properties of enrofloxacin in rabbits

Abstract

SUMMARY The pharmacokinetic properties of the fluoroquinolone antimicrobial enrofloxacina were studied in New Zealand White rabbits. Four rabbits were each given enrofloxacin as a single 5 mg/kg of body weight dosage by iv, sc, and oral routes over 4 weeks. Serum antimicrobial concentrations were determined for 24 hours after dosing. Compartmental modeling of the iv administration indicated that a 2-compartment open model best described the disposition of enrofloxacin in rabbits. Serum enrofloxacin concentrations after sc and oral dosing were best described by a 1- and 2-compartment model, respectively. Overall elimination half-lives for iv, sc, and oral routes of administration were 2.5, 1.71, and 2.41 hours, respectively. The half-life of absorption for oral dosing was 26 times the half-life of absorption after sc dosing (7.73 hours vs 0.3 hour). The observed time to maximal serum concentration was 0.9 hour after sc dosing and 2.3 hours after oral administration. The observed serum concentrations at these times were 2.07 and 0.452 μg/ml, respectively. Mean residence times were 1.55 hours for iv injections, 1.46 hours for sc dosing, and 8.46 hours for oral administration. Enrofloxacin was widely distributed in the rabbit as suggested by the volume of distribution value of 2.12 L/kg calculated from the iv study. The volume of distribution at steady-state was estimated at 0.93 L/kg. Compared with iv administration, bioavailability was 77% after sc dosing and 61% for gastrointestinal absorption. Estimates of predicted average steady-state serum concentrations were 0.359, 0.254, and 0.226 μg/ml for iv, sc, and oral administration, respectively. On the basis of maintaining enrofloxacin serum concentrations at 4 times the minimal inhibitory concentration90 for Pasteurella multocida, oral dosing resulted in the longest maximal time interval between doses of 15.4 hours vs 9.9 hours and 7.4 hours for iv and sc injections, respectively. Because enrofloxacin is widely dispersed in the rabbit's body, it is estimated from the data in this study that in vivo inhibitory concentrations of enrofloxacin for Pasteurella multocida may be maintained at oral dosage regimens equivalent to 5 mg/kg (q 12 h).