Bioequivalence Comparison of Seventeen Commercial Oral Enrofloxacins against the Original Pioneer Preparation in Broilers

Abstract

Considering the importance of fluoroquinolones in animal health and the fact that the enrofloxacin patent has expired, a bioequivalence study of seventeen preparations of enrofloxacin vs. the reference preparation (Baytril®) in broilers was carried out. Oral pharmacokinetics of seventeen commercial enrofloxacin preparations and Baytril as reference preparation were assessed in five trials in a total of 1760 broilers. Ten mg/kg of each preparation was administered to a total of 80 clinically healthy 3 weeks old broilers. After drug administration, blood was collected 8 times from ten birds within 24h. Using a microbiological agar diffusion analysis, serum concentration of enrofloxacin and metabolites were determined by correlating the composite antibacterial activity of enrofloxacin and metabolites with actual concentration. Bioequivalence limits were set between 80 to 125% reference values for maximum serum concentration (Csmax) and area under the curve (AUC). Results display mean Baytril® values of Csmax=1.662μg/ml±0.034 ; AUC=4.073±0.814μg/ml/hr. Only three preparations out of seventeen could be regarded as bioequivalent while the rest gave AUC and/or Csmax values smaller than the accepted lower limit of the mean values obtained for the reference enrofloxacin (P<0.05). The use of non-bioequivalent preparations of enrofloxacin will consequently undermine clinical outcomes and could play a significant role in accelerating the emergence of bacterial resistance in the poultry industry.

Keywords

• bioequivalence
• broilers
• enrofloxacin