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 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 faciliatate the administration of appropriate doses of ENR to all animals.