{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/105733"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/105733","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"Evaluation of the pharmacokinetics, pharmacodynamics, and safety of enrofloxacin administration to pregnant mares","abstract":"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.","abstract_html":"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.","abstract_has_math":false,"creators":["Ellerbrock, Robyn Elliene"],"institution":"University of Illinois at Urbana-Champaign","degree_name":"Ph.D.","degree_level":"Dissertation","degree_discipline":"VMS - Comparative Biosciences","degree_department":null,"school":null,"contributors":["Canisso, Igor","Ko, Jay","Bagchi, Indrani","Kline, Kevin","Shipley, Clifford","Lima, Fabio"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2019,"date_issued":"2019-11-26T20:48:57Z","date_published":"2019-11-26T20:48:57Z","updated_at":"2026-07-22T22:24:45Z","subjects":["enrofloxacin","ciprofloxacin","equine","pregnancy","cartilage"],"languages":["en"],"rights":["Copyright 2019 Robyn Ellerbrock"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/2142/105733","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Canisso, Igor","Ko, Jay","Bagchi, Indrani","Kline, Kevin","Shipley, Clifford","Lima, Fabio"]},{"key":"dc:creator","label":"Author","values":["Ellerbrock, Robyn Elliene"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2019-11-26T20:48:57Z","2021-11-27T10:15:26Z","2019-05-29","2019-08"]},{"key":"dc:type","label":"Dc Type","values":["text"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["VMS - Comparative Biosciences"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Ph.D."]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["University of Illinois at Urbana-Champaign"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["enrofloxacin","ciprofloxacin","equine","pregnancy","cartilage"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]},{"key":"dc:rights","label":"Dc Rights","values":["Copyright 2019 Robyn Ellerbrock"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/2142/105733"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["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.","Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2021-08-01","The student, Robyn Ellerbrock, accepted the attached license on 2019-04-18 at 07:49.","The student, Robyn Ellerbrock, submitted this Dissertation for approval on 2019-04-18 at 09:24.","This Dissertation was approved for publication on 2019-05-29 at 10:39.","DSpace SAF Submission Ingestion Package generated from Vireo submission #13715 on 2019-11-26 at 13:00:32","Made available in DSpace on 2019-11-26T20:48:57Z (GMT). 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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.","Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2021-08-01","The student, Robyn Ellerbrock, accepted the attached license on 2019-04-18 at 07:49.","The student, Robyn Ellerbrock, submitted this Dissertation for approval on 2019-04-18 at 09:24.","This Dissertation was approved for publication on 2019-05-29 at 10:39.","DSpace SAF Submission Ingestion Package generated from Vireo submission #13715 on 2019-11-26 at 13:00:32","Made available in DSpace on 2019-11-26T20:48:57Z (GMT). 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