title: Physicochemical characterization and pharmacokinetics in broiler chickens of a new recrystallized enrofloxacin hydrochloride dihydrate.
abstract: 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 (enroC ). 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 (enroR ) and enroC 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 ± 0.42 μg/mL for enroR and enroC , respectively; mean residence time was increased from 5.50 ± 0.26 h to 6.20 ± 0.71 h and the relative bioavailability of enroC was 336%. Considering Cmax /MIC and AUC/MIC ratios and the MIC values for a wild-type Escherichia coli O78/H12 (0.25 μg/mL), optimal ratios will only be achieved by enroC (Cmax /MIC = 23.6 and AUC/MIC = 197.7 for enroC ; vs. Cmax /MIC = 10.4 and AUC/MIC = 78.1 for enroR ). Furthermore, enroC may provide in most cases mutant prevention concentrations (Cmax /MIC ≥ 16). Ready solubility of powder enroC in drinking water at concentrations regularly used (0.01%) to provide an additional advantage of enroC in the field. Further development of enroC is warranted before it can be recommended for clinical use in veterinary medicine.
authors.affiliation: Departamento de Fisiología y Farmacología, Facultad de Medicina Veterinaria y Zootecnia, Universidad Nacional Autónoma de México, Ciudad de México, México.
authors.forename: L
authors.initials: L
authors.lastname: Gutierrez
authors.forename: J E
authors.initials: JE
authors.lastname: Miranda-Calderon
authors.forename: P
authors.initials: P
authors.lastname: Garcia-Gutierrez
authors.forename: H
authors.initials: H
authors.lastname: Sumano
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002645:Chickens / Q000378:metabolism*; D003460:Crystallization; D000077422:Enrofloxacin; D024841:Fluoroquinolones / Q000737:chemistry / Q000493:pharmacokinetics*; D013058:Mass Spectrometry; D008958:Models, Molecular; D015394:Molecular Structure
chemical_list: D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D000077422:Enrofloxacin