Physicochemical characterization and pharmacokinetics in broiler chickens of a new recrystallized enrofloxacin hydrochloride dihydrate

Enrofloxacin, a key antimicrobial agent in commercial avian medicine, has limited bioavailability (60%). This prompted its chemical manipulation to yield a new solvate-recrystallized enrofloxacin hydrochloride dihydrate entity (enro(C)). Its chemical structure was characterized by means of mass spectroscopy, Fourier transformed infrared spectroscopy, X-ray powder diffraction, and thermal analysis. Comparative oral pharmacokinetics (PK) of reference enrofloxacin (enro(R)) and enro(C) in broiler chickens after oral administration revealed noticeable improvements in key parameters and PK/PD ratios. Maximum serum concentration values were 2.61 +/- 0.21 and 5.9 +/- 0.42g/mL for enro(R) and enro(C), respectively; mean residence time was increased from 5.50 +/- 0.26h to 6.20 +/- 0.71h and the relative bioavailability of enro(C) was 336%. Considering C-max/MIC and AUC/MIC ratios and the MIC values for a wild-type Escherichia coli O78/H12 (0.25g/mL), optimal ratios will only be achieved by enro(C) (C-max/MIC=23.6 and AUC/MIC=197.7 for enro(C); vs. C-max/MIC=10.4 and AUC/MIC=78.1 for enro(R)). Furthermore, enro(C) may provide in most cases mutant prevention concentrations (C-max/MIC16). Ready solubility of powder enro(C) in drinking water at concentrations regularly used (0.01%) to provide an additional advantage of enro(C) in the field. Further development of enro(C) is warranted before it can be recommended for clinical use in veterinary medicine.