Comparative Pharmacokinetics of Intravenous Enrofloxacin in One- Six- And Twelve-Month-Old Sheep

Background: Enrofloxacin (ENR) is a fluoroquinolone antibiotic approved for use in sheep of all ages. The body composition and metabolic capability change with age. These changes may alter the pharmacokinetics of drugs and thus their effect. Therefore, the pharmacokinetics of drugs need to be established in target- age animals.Objective: To determine the pharmacokinetics of ENR and its active metabolite, ciprofloxacin (CIP), following a single intravenous administration of ENR at a dose of 10 mg/kg in different ages of sheep. Methods: The study was carried out in the one-, six- and twelve-month age period of the sheep. A single dose of 10 mg/kg ENR was administered intravenously through the jugular vein to sheep in all age periods. ENR and CIP plasma concentrations were determined using HPLC–UV and analyzed using a non-compartmental method. Results: ENR was detected in the plasma until 36 h in one-month-old and up to 24 h in other ages. CIP was detected in the plasma up to 24 h in all age groups. The t 1/2#142;zand V dsswere significantly higher in one-month-old sheep than in six and twelve-months old sheep. There was no difference in Cl Tand AUC values in different age groups. AUC 0-∞CIP/AUC 0-∞ENRratios were higher in one-month-old than in six- and twelve-months sheep. Conclusion: The most important pharmacokinetic changes associated with aging in sheep are decreased V dssand t 1/2#142;zof ENR and the low ratio metabolizing of ENR to CIP. Pharmacokinetic/pharmacodynamic data showed that ENR after IV administration of 10 mg/kg dose provided the optimal AUC 0–24/MIC 90ratios for E. coli, P. multocidaand Mycoplasmaspp. (>125) with MIC of 0.37 μg/mL and for S. aureus (>30) with MIC of 0.5 μg/mL in all ages of sheep.