Comparison of pharmacokinetics of danofloxacin and enrofloxacin in calves challenged with Mannheimia haemolytica.
OBJECTIVE
To compare concentrations of danofloxacin, enrofloxacin, and ciprofloxacin in plasma and respiratory tissues of calves treated after challenge with Mannheimia haemolytica.


METHODS
75 calves.


METHODS
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 (AUC(12h)-to-MIC) were calculat-ed.


RESULTS
Danofloxacin and enrofloxacin had MICs of 0.03 microg/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 AUC(12h)-to-MIC ratios >125 hours.


CONCLUSIONS
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.
TerHune
Terry N
TN
HMS Veterinary Development Inc, 3346 Ave 248, Tulare, CA 92374, USA.
Skogerboe
Terry L
TL
Shostrom
Valerie K
VK
Weigel
Daniel J
DJ
D000818:Animals; D000890:Anti-Infective Agents / Q000493:pharmacokinetics*; D018893:Bronchoalveolar Lavage / Q000662:veterinary; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002417:Cattle; D002851:Chromatography, High Pressure Liquid / Q000662:veterinary; D002939:Ciprofloxacin / Q000493:pharmacokinetics; D000077422:Enrofloxacin; D024841:Fluoroquinolones / Q000493:pharmacokinetics*; D008168:Lung / Q000378:metabolism / Q000382:microbiology; D008297:Male; D016978:Mannheimia haemolytica / Q000472:pathogenicity*; D008826:Microbial Sensitivity Tests / Q000662:veterinary; D012766:Pasteurellosis, Pneumonic / Q000378:metabolism* / Q000382:microbiology; D015363:Quinolones / Q000493:pharmacokinetics*
D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D015363:Quinolones; C068581:danofloxacin; D000077422:Enrofloxacin; D002939:Ciprofloxacin