Pharmacokinetics and endometrial tissue concentrations of enrofloxacin and the metabolite ciprofloxacin after i.v. administration of enrofloxacin to mares

Abstract

Enrofloxacin was administered i.v. to five adult mares at a dose of 5 mg/kg. After administration, blood and endometrial biopsy samples were collected at regular intervals for 24 h. The plasma and tissue samples were analyzed for enrofloxacin and the metabolite ciprofloxacin by high‐pressure liquid chromatography. In plasma, enrofloxacin had a terminal half‐life (t_½), volume of distribution (area method), and systemic clearance of 6.7 ± 2.9 h, 1.9 ± 0.4 L/kg, and 3.7 ± 1.4 mL/kg/min, respectively. Ciprofloxacin had a maximum plasma concentration (C_max) of 0.28 ± 0.09 μg/mL. In endometrial tissue, the enrofloxacin C_max was 1.7 ± 0.5 μg/g, and the t_½ was 7.8 ± 3.7 h. Ciprofloxacin C_max in tissues was 0.15 ± 0.04 μg/g and the t_½ was 5.2 ± 2.0 h. The tissue:plasma enrofloxacin concentration ratios (w/w:w/v) were 0.175 ± 0.08 and 0.47 ± 0.06 for C_max and AUC, respectively. For ciprofloxacin, these values were 0.55 ± 0.13 and 0.58 ± 0.31, respectively. We concluded that plasma concentrations achieved after 5 mg/kg i.v. are high enough to meet surrogate markers for antibacterial activity (C_max:MIC ratio, and AUC:MIC ratio) considered effective for most susceptible gram‐negative bacteria. Endometrial tissue concentrations taken from the mares after dosing showed that enrofloxacin and ciprofloxacin both penetrate this tissue adequately after systemic administration and would attain concentrations high enough in the tissue fluids to treat infections of the endometrium caused by susceptible bacteria.