Comparative pharmacokinetics of enrofloxacin in mice, rats, rabbits, sheep, and cows

Abstract

Objective - To compare pharmacokinetic variables of enrofloxacin (ENR) after IV administration in mice, rats, rabbits, sheep, and cows and to perform allometric analysis of ENR. Animals - 47 mice, 5 rats, 5 rabbits, 5 sheep, and 5 cows. Procedure - Serially obtained plasma samples were assayed for ENR concentration, using high-performance liquid chromatography. In vitro plasma protein binding was determined by ultrafiltration. Plasma ENR concentration versus time curves were fitted by use of nonlinear least- squared regression analysis. Pharmacokinetic variables were correlated further with body weight. Results - In all species studied, the best fit was obtained for a two-compartment open model; ENR half-life ranged from 89 minutes in mice to 169 minutes in cows. Volume of distribution was large in all species studied, with values ranging from 10.5 L/kg in mice to 1.5 L/kg in sheep. Body clearance ranged from 68.1 ml/min/kg for mice to 4.6 ml/min/kg for sheep. Unbound ENR was found to be (mean ± SD) 58 ± 2, 50 ± 6, 50 ± 2, 31 ± 2, and 40 ± 3% in plasma of mice, rats, rabbits, sheep, and cows, respectively. The only pharmacokinetic variables that could be correlated with body weight were elimination half-life, clearance, and volume of distribution. Allometric exponents denoting proportionality of half-life, body clearance, and volume of distribution with body weight were 0.06, 0.82, and 0.90, respectively. Conclusions and Clinical Relevance - An allometric approach could provide a suitable method for determining a scale for ENR pharmacokinetics among various mammalian species. This would facilitate the administration of appropriate doses of ENR to all animals.