Comparison of pharmacokinetics of danofloxacin and enrofloxacin in calves challenged with Mannheimia haemolytica

Abstract

Objective - To compare concentrations of danofloxacin, enrofloxacin, and ciprofloxacin in plasma and respiratory tissues of calves treated after challenge with Mannheimia haemolytica. Animals - 75 calves. Procedure - 24 hours after challenge with M haemolytica, 72 calves with clinical signs of respiratory tract disease were randomly assigned to 1 of 12 equal treatment groups. Three nonchallenged, nontreated calves formed a control group. Challenged calves were treated with danofloxacin (6 and 8 mg/kg, SC) and enrofloxacin (8 mg/kg, SC) once. At 1, 2, 6, and 12 hours after treatment, 6 calves from each treatment group were euthanatized. Antimicrobial drug concentrations were assayed in various specimens. Peak plasma concentration (Cmax)-to-minimum inhibitory concentration (MIC; Cmax-to-MIC) ratios and the area under the concentration versus time curve over a 12-hour period-to-MIC ratios (AUC12h-to-MIC) were calculated. Results - Danofloxacin and enrofloxacin had MICs of 0.03 μg/mL for the M haemolytica challenge isolate. Danofloxacin administered at doses of 6 and 8 mg/kg resulted in numerically higher geometric mean concentrations of danofloxacin in plasma and all respiratory tissues than geometric mean concentrations of enrofloxacin after treatment with enrofloxacin. Geometric mean concentrations of enrofloxacin were numerically higher than geometric mean concentrations of ciprofloxacin metabolite in plasma and almost all respiratory tissues. Danofloxacin and enrofloxacin achieved Cmax-to-MIC ratios > 10 and AUC12h-to-MIC ratios > 125 hours. Conclusions and Clinical Relevance - When used to treat pneumonic pasteurellosis in calves, danofloxacin and enrofloxacin can be expected to deliver concentration-dependent bactericidal activity against M haemolytica, the bacteria most commonly associated with bovine respiratory tract disease.