Comparative pharmacokinetics of two florfenicol formulations following intramuscular and subcutaneous administration to sheep

Christie C. Balcomb William R. Pritchard Veterinary Medical Teaching Hospital, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616

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John A. Angelos Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616

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Munashe Chigerwe Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616

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Barbara A. Byrne Department of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616

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V. Michael Lane Department of Population Health and Reproduction, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616

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Scott E. Wetzlich Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616

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Orhan Sahin Department of Veterinary Diagnostic and Production Animal Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA 50011

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Larry Holler Department of Veterinary and Biomedical Sciences, College of Agriculture and Biological Sciences, South Dakota State University, Brookings, SD 57077

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Shuping Zhang Veterinary Medical Diagnostic Laboratory, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211

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Lisa A. Tell Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616

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Abstract

OBJECTIVE To compare the pharmacokinetics of 2 commercial florfenicol formulations following IM and SC administration to sheep.

ANIMALS 16 healthy adult mixed-breed sheep.

PROCEDURES In a crossover study, sheep were randomly assigned to receive florfenicol formulation A or B at a single dose of 20 mg/kg, IM, or 40 mg/kg, SC. After a 2-week washout period, each sheep was administered the opposite formulation at the same dose and administration route as the initial formulation. Blood samples were collected immediately before and at predetermined times for 24 hours after each florfenicol administration. Plasma florfenicol concentrations were determined by high-performance liquid chromatography. Pharmacokinetic parameters were estimated by noncompartmental methods and compared between the 2 formulations at each dose and route of administration.

RESULTS Median maximum plasma concentration, elimination half-life, and area under the concentration-time curve from time 0 to the last quantifiable measurement for florfenicol were 3.76 μg/mL, 13.44 hours, and 24.88 μg•h/mL, respectively, for formulation A and 7.72 μg/mL, 5.98 hours, and 41.53 μg•h/mL, respectively, for formulation B following administration of 20 mg of florfenicol/kg, IM, and 2.63 μg/mL, 12.48 hours, and 31.63 μg•h/mL, respectively, for formulation A and 4.70 μg/mL, 16.60 hours, and 48.32 μg•h/mL, respectively, for formulation B following administration of 40 mg of florfenicol/kg, SC.

CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that both formulations achieved plasma florfenicol concentrations expected to be therapeutic for respiratory tract disease caused by Mannheimia haemolytica or Pasteurella spp at both doses and administration routes evaluated.

Abstract

OBJECTIVE To compare the pharmacokinetics of 2 commercial florfenicol formulations following IM and SC administration to sheep.

ANIMALS 16 healthy adult mixed-breed sheep.

PROCEDURES In a crossover study, sheep were randomly assigned to receive florfenicol formulation A or B at a single dose of 20 mg/kg, IM, or 40 mg/kg, SC. After a 2-week washout period, each sheep was administered the opposite formulation at the same dose and administration route as the initial formulation. Blood samples were collected immediately before and at predetermined times for 24 hours after each florfenicol administration. Plasma florfenicol concentrations were determined by high-performance liquid chromatography. Pharmacokinetic parameters were estimated by noncompartmental methods and compared between the 2 formulations at each dose and route of administration.

RESULTS Median maximum plasma concentration, elimination half-life, and area under the concentration-time curve from time 0 to the last quantifiable measurement for florfenicol were 3.76 μg/mL, 13.44 hours, and 24.88 μg•h/mL, respectively, for formulation A and 7.72 μg/mL, 5.98 hours, and 41.53 μg•h/mL, respectively, for formulation B following administration of 20 mg of florfenicol/kg, IM, and 2.63 μg/mL, 12.48 hours, and 31.63 μg•h/mL, respectively, for formulation A and 4.70 μg/mL, 16.60 hours, and 48.32 μg•h/mL, respectively, for formulation B following administration of 40 mg of florfenicol/kg, SC.

CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that both formulations achieved plasma florfenicol concentrations expected to be therapeutic for respiratory tract disease caused by Mannheimia haemolytica or Pasteurella spp at both doses and administration routes evaluated.

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