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(1/2)), 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 (Cmax) of 0.28 +/- 0.09 microg/mL. In endometrial tissue, the enrofloxacin Cmax was 1.7 +/- 0.5 microg/g, and the t(1/2) was 7.8 +/- 3.7 h. Ciprofloxacin Cmax in tissues was 0.15 +/- 0.04 microg/g and the t(1/2) 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 Cmax 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 (Cmax: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.

Effects of Intrauterine Infusion of a Water-Based Suspension of Enrofloxacin on Mare Endometrium

“…Plasma and endometrial samples from an untreated mare served as a control. All samples were analyzed by high-performance liquid chromatography (HPLC) at the College of Veterinary Medicine, North Carolina State University (Dr M. Papich) [13].…”

Altered pharmacokinetics of enrofloxacin in experimental models of hepatic and renal impairment

“…The rates of its metabolic conversion were variable in several species. Richez et al (1994) and Papich et al (2002) reported that enrofloxacin was metabolized to ciprofloxacin by 25% and 17% in cattle and horses, as calculated from the ratio between the AUCs of ciprofloxacin and enrofloxacin. In dogs and cats, the metabolite formation was determined 20 and 10% of C max , respectively Richez et al 1997).…”

Reproductive Tract Infections in Horses

“…Enrofloxacin concentrations remained greater than the MIC for a sensitive E coli strain for 24 hours [113]. Investigation of intravenous administration of enrofloxacin at a dose of 5 mg/kg revealed adequate endometrial concentrations of enrofloxacin and its metabolite ciprofloxacin to treat infection with susceptible bacteria [114]. The systemic distribution of another fluoroquinolone, orbifloxacin, was also investigated [115].…”

“…Requirements for systemically administered drug penetration into the genital tract include bases with high lipid solubility and high pKa. Although not licensed for use in the horse, fluoroquinolones seem to have these favorable characteristics [114]. They have been shown to penetrate endometrial tissue and achieve concentrations sufficient to treat susceptible organisms.…”