Pharmaceutical Design of a Formulation of Enrofloxacin-Alginate and its Strategic Dosage to Achieve Mutant Prevention PK/PD Ratios in Broiler Chickens

Abstract

Introduction: The comparative pharmacokinetics (PK) and PK/pharmacodynamics (PD) ratios of a new pharmaceutical design of enrofloxacin-alginate in dried beads (EADBs) and the reference enrofloxacin 10% solution was determined in broiler chickens. Also, the same parameters were determined after administering enrofloxacin with a double dosing scheme (through drinking water and as an in-feed medication of EADBs). 500 Arbor-Acres broiler chickens were randomly divided into five groups (n=100), adjusting in all cases, a dose of 10 mg/kg based on water and feed intake as follows: group EADBsad-lib receiving enrofloxacin through EADBs added to their feed as dressing; group EADBsbolus forcing the beads into the proventriculus using a semi-rigid gavage; group Enroad-lib dosed through their drinking water; group Enrobolus also administered into the proventriculus by gavage; group Enrow&f administering 5 mg/kg as EADBs in their feed, plus 5 mg/kg of enrofloxacin through their drinking water. Methods: The PK parameters and the key PK/PD ratios were determined (Cmax/MIC and AUC0-24/MIC). Only group Enrow&f could achieve the PK/PD ratios regarded as mutant-prevention. Results: This trial is the first one in which an in-feed medication of enrofloxacin, combined with water dosing, can result in PK/PD parameters superior to those obtained after administering the drug through drinking water at a dose of 10 mg/kg. Conclusion: Contrary to expectations, groups Enroad-lib and Enrobolus failed to achieve the desired PK/PD ratios when the breakpoint was established at 0.5 μg/mL but did so when MIC was set at 0.1 μg/mL. In contrast, EADBsbolus and Enrow&f achieved an adequate AUC0-24/MIC ratio for both MIC levels.