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Equine Vet J. 2019 Jul;51(4):544-551. doi: 10.1111/evj.13044. Epub 2019 Jan 2.

Diffusion of enrofloxacin to pregnancy fluids and effects on fetal cartilage after intravenous administration to late pregnant mares.

Author information

1
Department of Veterinary Clinical Medicine, College of Veterinary Medicine, University of Illinois Urbana Champaign, Urbana, Illinois, USA.
2
Department of Comparative Biosciences, College of Veterinary Medicine, University of Illinois Urbana Champaign, Urbana, Illinois, USA.
3
Roy J. Carver Biotechnology Center, University of Illinois Urbana-Champaign, Urbana, Illinois, USA.

Abstract

BACKGROUND:

In selective cases, enrofloxacin may be an alternative antibacterial agent to treat unresponsive infections in pregnant mares. Supratherapeutic doses of enrofloxacin are toxic to adult horses and also to newborn foals, however, it is unknown if enrofloxacin crosses the equine placenta or if it is toxic to the fetus.

OBJECTIVES:

To assess the diffusion of enrofloxacin and its metabolite to fetal fluids and its effects on fetal cartilage when administered to pregnant mares.

STUDY DESIGN:

In vivo and terminal controlled experiment.

METHODS:

Healthy mares at 260 days of gestation were allocated into three groups: untreated (n = 3), therapeutic treatment (5 mg/kg enrofloxacin, i.v., n = 7) or supratherapeutic treatment (10 mg/kg, i.v., n = 6) for 11 days. Fetal fluids were collected on days 1, 5 and 11 of treatment. Premature delivery was induced on day 11 with oxytocin and fetal fluids and plasma were collected during delivery. Plasma and fetal fluid enrofloxacin and ciprofloxacin concentrations were measured by liquid chromatography-mass spectrometry. Fetal articular cartilage was examined macroscopically and histologically for lesions.

RESULTS:

Enrofloxacin and ciprofloxacin reached the minimum inhibitory concentrations for common pathogens in all fluids. Ciprofloxacin did not increase with the double enrofloxacin dose in maternal plasma, but allantoic fluid showed a 10-fold increase relative to fetal trough plasma concentrations. Administration of enrofloxacin at recommended doses did not result in cartilaginous lesions in fetuses.

MAIN LIMITATIONS:

Only one time point in gestation was evaluated and mares treated in the study were healthy at the time of treatment. It remains to be determined if enrofloxacin shows toxicity at other stages of pregnancy, after a longer duration of treatment, or once the foals are delivered and articular surfaces are weightbearing.

CONCLUSIONS:

Short-term administration of enrofloxacin to late gestation mares resulted in detectable enrofloxacin and ciprofloxacin concentrations in fetal fluids and did not result in macroscopic or microscopic lesions in the fetus. While further research is needed to address long-term foal outcomes, enrofloxacin may be useful for select bacterial infections in pregnant mares.

KEYWORDS:

LC-MS/MS; ciprofloxacin; fetal toxicity; fluoroquinolone; horse

PMID:
30449030
DOI:
10.1111/evj.13044
[Indexed for MEDLINE]

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