Pharmacokinetics of ceftiofur crystalline-free acid following subcutaneous administration of a single dose to sheep

Sarai Rivera-Garcia William R. Pritchard Veterinary Medical Teaching Hospital, College of Agricultural and Environmental Sciences, University of California-Davis, Davis, CA 95616.

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John A. Angelos Department of Medicine and Epidemiology, College of Agricultural and Environmental Sciences, University of California-Davis, Davis, CA 95616.

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Joan D. Rowe Department of Population Health and Reproduction, College of Agricultural and Environmental Sciences, University of California-Davis, Davis, CA 95616.

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Barbara A. Byrne Department of Pathology, Microbiology, and Immunology, College of Agricultural and Environmental Sciences, University of California-Davis, Davis, CA 95616.

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Scott E. Wetzlich Department of Medicine and Epidemiology, College of Agricultural and Environmental Sciences, University of California-Davis, Davis, CA 95616.

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Dana B. Van Liew School of Veterinary Medicine, and the Department of Animal Science, College of Agricultural and Environmental Sciences, University of California-Davis, Davis, CA 95616.

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Lisa A. Tell Department of Medicine and Epidemiology, College of Agricultural and Environmental Sciences, University of California-Davis, Davis, CA 95616.

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Abstract

Objective—To determine the pharmacokinetics of ceftiofur crystalline-free acid (CCFA) following SC administration of a single dose to sheep.

Animals—9 healthy adult female Suffolk-crossbred sheep.

Procedures—Each sheep was administered 6.6 mg of CCFA/kg, SC, in the cervical region once. Serial blood samples were collected at predetermined intervals for 14 days. Serum concentration of ceftiofur free-acid equivalents (CFAE) was determined by high-performance liquid chromatography. Pharmacokinetic parameters were determined by compartmental and noncompartmental methods.

Results—Pharmacokinetics for CCFA following SC administration in sheep was best described with a 1-compartment model. Mean ± SD area under the concentration-time curve from time 0 to infinity, peak serum concentration, and time to peak serum concentration were 206.6 ± 24.8 μ•h/mL, 2.4 ± 0.5 μg/mL, and 23.1 ± 10.1 h, respectively. Serum CFAE concentrations ≥ 1 μg/mL (the target serum CFAE concentration for treatment of disease caused by Mannheimia haemolytica and Pasteurella multocida) were maintained for 2.6 to 4.9 days. No significant adverse reactions to CCFA administration were observed.

Conclusions and Clinical Relevance—Results indicated that adequate therapeutic serum concentrations of CFAE for treatment of disease caused by M haemolytica and P multocida were achieved in sheep following SC administration of a single dose (6.6 mg/kg) of CCFA. Thus, CCFA might be useful for the treatment of common respiratory tract pathogens in sheep.

Abstract

Objective—To determine the pharmacokinetics of ceftiofur crystalline-free acid (CCFA) following SC administration of a single dose to sheep.

Animals—9 healthy adult female Suffolk-crossbred sheep.

Procedures—Each sheep was administered 6.6 mg of CCFA/kg, SC, in the cervical region once. Serial blood samples were collected at predetermined intervals for 14 days. Serum concentration of ceftiofur free-acid equivalents (CFAE) was determined by high-performance liquid chromatography. Pharmacokinetic parameters were determined by compartmental and noncompartmental methods.

Results—Pharmacokinetics for CCFA following SC administration in sheep was best described with a 1-compartment model. Mean ± SD area under the concentration-time curve from time 0 to infinity, peak serum concentration, and time to peak serum concentration were 206.6 ± 24.8 μ•h/mL, 2.4 ± 0.5 μg/mL, and 23.1 ± 10.1 h, respectively. Serum CFAE concentrations ≥ 1 μg/mL (the target serum CFAE concentration for treatment of disease caused by Mannheimia haemolytica and Pasteurella multocida) were maintained for 2.6 to 4.9 days. No significant adverse reactions to CCFA administration were observed.

Conclusions and Clinical Relevance—Results indicated that adequate therapeutic serum concentrations of CFAE for treatment of disease caused by M haemolytica and P multocida were achieved in sheep following SC administration of a single dose (6.6 mg/kg) of CCFA. Thus, CCFA might be useful for the treatment of common respiratory tract pathogens in sheep.

Contributor Notes

Dr. Rivera-Garcia's present address is USDA Food Safety and Inspection Service, Philadelphia District Office, Mellon Independence Center, 701 Market St, Ste 4100A, Philadelphia, PA 19106.

Supported by the Minor Use Animal Drug Program (National Research Support Project No. 7) and the University of California-Davis School of Veterinary Medicine Faculty Discretionary Fund.

The views and conclusions contained in this document are those of the authors and should not be interpreted as necessarily representing the official policies, expressed or implied, of the USDA Food Safety and Inspection Service.

Presented in abstract form at the University of California-Davis House Officer Seminar Day, Davis, Calif, March 2011; and at the 2011 American College of Veterinary Internal Medicine Forum, Denver, June 2011.

The authors thank Hung Kieu, Jennifer Lutze, Jessica Sampson and Drs. Meera Heller, Tara Marmulak, Juan C. Pavez, Natalia Martinez, Catalina Cabrera, and Vengai Mavangira for technical assistance.

Address correspondence to Dr. Tell (latell@ucdavis.edu).
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