The influence of age and body weight gain on enrofloxacin pharmacokinetics in turkeys-Allometric approach to dose optimization.

Abstract

Enrofloxacin is a concentration-dependent antimicrobial used in bacterial infections in poultry. During a few months of a turkey's life, pharmacokinetics of drugs undergoes substantial changes which may compromise their efficacy due to variability in internal exposure (measured by area under the concentration-time curve, AUC). The aim of this study was to describe the effects of age on the pharmacokinetics of a single intravenous (i.v.) and oral administration of enrofloxacin at a dose of 10mg/kg to turkeys. It was found that during a 2.5-month-long period of growth from 1.4 to 14.6kg, the AUC after i.v. administration increased almost threefold due to a significant decrease in the body clearance (from a mean of 0.76-0.28 Lhr-1 kg-1 ). Over the same period, the mean elimination half-life was prolonged from 2.65 to 7.03hr. Oral administration resulted in a similar trend in pharmacokinetic parameters. For both routes, formation of the major metabolite, ciprofloxacin, was marginal. Protein binding was not age-dependent and never exceeded 50%. Body clearance, volume of distribution and elimination half-life were subjected to an allometric analysis and a novel, nonlinear dosage protocol has been proposed to improve the internal exposure to the drug in different age groups of turkeys.