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Comparative pharmacokinetics of enrofloxacin in mice, rats, rabbits, sheep, and cows
M A Bregante1, P Saez, J J Aramayona
1Department of Pharmacology and Physiology, School of Veterinary Science, University of Zaragoza, Spain.
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.