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

Objective-To compare pharmacokinetic variables of enrofloxacin (ENR) after IV administration in mice, rats, rabbits, sheep, and cows and to perform al lometric analysis of ENR. Animals-47 mice, 5 rats, 5 rabbits, 5 sheep, and 5 cows. Procedure-Serially obtained plasma samples were assayed for ENR concentrati on, using high-performance liquid chromatography. In vitro plasma protein b inding was determined by ultrafiltration. Plasma ENR concentration versus t ime curves were fitted by use of nonlinear least-squared regression analysi s. Pharmacokinetic variables were correlated further with body weight. Results-in all species studied, the best fit was obtained for a two-compart ment open model; ENR half-life ranged from 89 minutes in mice to 169 minute s in cows. Volume of distribution was large in all species studied, with va lues ranging from 10.5 L/kg in mice to 1.5 L/kg in sheep. Body clearance ra nged from 68.1 ml/min/kg for mice to 4.6 ml/min/kg for sheep. Unbound ENR w as 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. Th e only pharmacokinetic variables that could be correlated with body weight were elimination half-life, clearance, and volume of distribution. Allometr ic exponents denoting proportionality of half-life, body clearance, and vol ume of distribution with body weight were 0.06, 0.82, and 0.90, respectivel y. Conclusions and Clinical Relevance-An allometric approach could provide a s uitable method for determining a scale for ENR pharmacokinetics among vario us mammalian species. This would faciliatate the administration of appropri ate doses of ENR to all animals.