Evaluation of the pharmacokinetics, pharmacodynamics, and safety of enrofloxacin administration to pregnant mares

Antimicrobial therapy is necessary in pregnant mares affected by severe bacterial infections such as cellulitis, bronchopneumonia, or placentitis. Despite the many antimicrobials available for human use, very few antimicrobials are cost-effective and approved for use in the horse. Enrofloxacin is a fluoroquinolone antibiotic that is available in both oral and intravenous formulations and is commonly used in veterinary medicine. This fluoroquinolone acts by inhibiting bacterial DNA synthesis. Previous work suggests that the neonatal animal is sensitive to fluoroquinolones, and that exposure during development will affect cartilage in the neonate. However, fluoroquinolones are used in some pregnant species without obvious effects on the fetus. To understand potential toxic effects on the fetus, the pharmacokinetics and pharmacodynamics of the enrofloxacin in both the intravenous form and a newer oral form were evaluated in the pregnant mare. After determining the optimal dose, and a higher dose that might be used to treat intermediately susceptible bacteria, mares were treated with intravenous enrofloxacin at 260 days gestation. Both enrofloxacin and its active metabolite ciprofloxacin crossed the placenta, and reached therapeutic levels in the fetus and fetal fluids, without apparent effects on the fetus. Next, to explore long-term effects of enrofloxacin on fetal development, mares were treated for 14 days at 280 days gestation, and allowed to foal. Foal cartilage and tendon strength were then evaluated at 30 days of age, and no effects of treatment were observed on gross or histologic examination. In contrast, foals treated with enrofloxacin at 14 days postnatally developed clinical lameness and moderate to severe lesions on histopathology. All foals were then subjected to additional testing to determine if normal veterinary assessments were insufficient to detect long term effects of mild in utero toxicity. Structural MRI, qMRI and RT-PCR analysis failed to detect changes in cartilage properties in the in utero-exposed animals. Overall, it is proposed that enrofloxacin and its active metabolite ciprofloxacin cross the equine placenta and reach the equine fetus at therapeutic concentrations. At therapeutic doses, exposure to these fluoroquinolones in utero during the first or third trimesters does not appear to cause either acute, or chronic cartilaginous lesions in the developing fetus.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

VMS - Comparative Biosciences

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2019

Author dc:creator

• Ellerbrock, Robyn Elliene

Contributors dc:contributor

• Canisso, Igor
• Ko, Jay
• Bagchi, Indrani
• Kline, Kevin
• Shipley, Clifford
• Lima, Fabio

• enrofloxacin
• ciprofloxacin
• equine
• pregnancy
• cartilage

Statement dc:rights

• Copyright 2019 Robyn Ellerbrock

Language dc:language

en

Handle dc:identifier

http://hdl.handle.net/2142/105733

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/105733