Pharmacokinetics of pradofloxacin, florfenicol, and tulathromycin and response to treatment of steers experimentally infected with Mannheimia hemolytica

Abstract Background Bovine respiratory disease (BRD) is an economically important disease in the beef industry, and a major driver of therapeutic antibiotic use. Pharmacokinetic data of these drugs is relatively limited in diseased animals. Hypothesis/Objective To determine the concentrations of pra...

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Main Authors: Derek M. Foster, Jennifer L. Halleran, Megan E. Jacob, Stephanie Hempstead, Luke B. Borst, Tatiane T. Negrao Watanabe, Hiroko Enomoto, Mark G. Papich
Format: Article
Language:English
Published: Wiley 2025-01-01
Series:Journal of Veterinary Internal Medicine
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Online Access:https://doi.org/10.1111/jvim.17270
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author Derek M. Foster
Jennifer L. Halleran
Megan E. Jacob
Stephanie Hempstead
Luke B. Borst
Tatiane T. Negrao Watanabe
Hiroko Enomoto
Mark G. Papich
author_facet Derek M. Foster
Jennifer L. Halleran
Megan E. Jacob
Stephanie Hempstead
Luke B. Borst
Tatiane T. Negrao Watanabe
Hiroko Enomoto
Mark G. Papich
author_sort Derek M. Foster
collection DOAJ
description Abstract Background Bovine respiratory disease (BRD) is an economically important disease in the beef industry, and a major driver of therapeutic antibiotic use. Pharmacokinetic data of these drugs is relatively limited in diseased animals. Hypothesis/Objective To determine the concentrations of pradofloxacin, florfenicol, and tulathromycin in the airways, plasma, and interstitial fluid (ISF) of steers with a clinically relevant model of bacterial respiratory disease. Animals Twenty‐four Holstein and Holstein/Jersey cross steers ranging in age from 6 to 15 months. Methods A randomized, blinded clinical trial was performed. After transport stress, steers were inoculated with Mannheimia hemolytica to induce BRD. Upon onset of clinical disease, steers were treated with pradofloxacin, florfenicol or tulathromycin. Blood, ISF, and pulmonary epithelial lining fluid (PELF) samples were obtained for drug concentration determination. Clinical exams and thoracic ultrasound examinations were conducted daily. Animals were euthanized at the end of the study period to assess lung lesions. Results Pradofloxacin Cmax in PELF was 0.81 μg/mL (CV = 49.02%) and penetration into the PELF was 203.58% (72%). Florfenicol Cmax in PELF was 2.94 μg/mL (42.1%) and penetration was 230.08% (78.82%). Tulathromycin PELF Cmax was 0.9 μg/mL (45.03%) and PELF penetration was 518.97% (56.59%). Conclusions and Clinical Importance There are differences in penetration of the drugs into the ISF and PELF compared to one another and previous data from healthy steers demonstrating the effect of disease on the PK of these drugs.
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spelling doaj-art-4f1992d25e834250942690079967b3312025-01-27T15:22:41ZengWileyJournal of Veterinary Internal Medicine0891-66401939-16762025-01-01391n/an/a10.1111/jvim.17270Pharmacokinetics of pradofloxacin, florfenicol, and tulathromycin and response to treatment of steers experimentally infected with Mannheimia hemolyticaDerek M. Foster0Jennifer L. Halleran1Megan E. Jacob2Stephanie Hempstead3Luke B. Borst4Tatiane T. Negrao Watanabe5Hiroko Enomoto6Mark G. Papich7Department of Population Health and Pathobiology, College of Veterinary Medicine North Carolina State University Raleigh North Carolina USADepartment of Population Health and Pathobiology, College of Veterinary Medicine North Carolina State University Raleigh North Carolina USADepartment of Population Health and Pathobiology, College of Veterinary Medicine North Carolina State University Raleigh North Carolina USADepartment of Population Health and Pathobiology, College of Veterinary Medicine North Carolina State University Raleigh North Carolina USAAntech Diagnostics, Inc. Phoenix Arizona USAAntech Diagnostics, Inc. Phoenix Arizona USADepartment of Population Health and Pathobiology, College of Veterinary Medicine North Carolina State University Raleigh North Carolina USADepartment of Molecular and Biomedical Sciences, College of Veterinary Medicine North Carolina State University Raleigh North Carolina USAAbstract Background Bovine respiratory disease (BRD) is an economically important disease in the beef industry, and a major driver of therapeutic antibiotic use. Pharmacokinetic data of these drugs is relatively limited in diseased animals. Hypothesis/Objective To determine the concentrations of pradofloxacin, florfenicol, and tulathromycin in the airways, plasma, and interstitial fluid (ISF) of steers with a clinically relevant model of bacterial respiratory disease. Animals Twenty‐four Holstein and Holstein/Jersey cross steers ranging in age from 6 to 15 months. Methods A randomized, blinded clinical trial was performed. After transport stress, steers were inoculated with Mannheimia hemolytica to induce BRD. Upon onset of clinical disease, steers were treated with pradofloxacin, florfenicol or tulathromycin. Blood, ISF, and pulmonary epithelial lining fluid (PELF) samples were obtained for drug concentration determination. Clinical exams and thoracic ultrasound examinations were conducted daily. Animals were euthanized at the end of the study period to assess lung lesions. Results Pradofloxacin Cmax in PELF was 0.81 μg/mL (CV = 49.02%) and penetration into the PELF was 203.58% (72%). Florfenicol Cmax in PELF was 2.94 μg/mL (42.1%) and penetration was 230.08% (78.82%). Tulathromycin PELF Cmax was 0.9 μg/mL (45.03%) and PELF penetration was 518.97% (56.59%). Conclusions and Clinical Importance There are differences in penetration of the drugs into the ISF and PELF compared to one another and previous data from healthy steers demonstrating the effect of disease on the PK of these drugs.https://doi.org/10.1111/jvim.17270antibioticsbovine respiratory diseasefluoroquinolone
spellingShingle Derek M. Foster
Jennifer L. Halleran
Megan E. Jacob
Stephanie Hempstead
Luke B. Borst
Tatiane T. Negrao Watanabe
Hiroko Enomoto
Mark G. Papich
Pharmacokinetics of pradofloxacin, florfenicol, and tulathromycin and response to treatment of steers experimentally infected with Mannheimia hemolytica
Journal of Veterinary Internal Medicine
antibiotics
bovine respiratory disease
fluoroquinolone
title Pharmacokinetics of pradofloxacin, florfenicol, and tulathromycin and response to treatment of steers experimentally infected with Mannheimia hemolytica
title_full Pharmacokinetics of pradofloxacin, florfenicol, and tulathromycin and response to treatment of steers experimentally infected with Mannheimia hemolytica
title_fullStr Pharmacokinetics of pradofloxacin, florfenicol, and tulathromycin and response to treatment of steers experimentally infected with Mannheimia hemolytica
title_full_unstemmed Pharmacokinetics of pradofloxacin, florfenicol, and tulathromycin and response to treatment of steers experimentally infected with Mannheimia hemolytica
title_short Pharmacokinetics of pradofloxacin, florfenicol, and tulathromycin and response to treatment of steers experimentally infected with Mannheimia hemolytica
title_sort pharmacokinetics of pradofloxacin florfenicol and tulathromycin and response to treatment of steers experimentally infected with mannheimia hemolytica
topic antibiotics
bovine respiratory disease
fluoroquinolone
url https://doi.org/10.1111/jvim.17270
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