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Pharmacokinetics of a long-acting ceftiofur crystalline-free acid formulation in Asian elephants (Elephas maxim us)

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  • 1 Saint Louis Zoo, 1 Government Dr, St Louis, MO 63110.
  • | 2 Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211.
  • | 3 Saint Louis Zoo, 1 Government Dr, St Louis, MO 63110.
  • | 4 Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996.
  • | 5 Clinical Pharmacology Laboratory, Department of Comparative Medicine, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996.

Abstract

Objective—To determine the pharmacokinetics of a long-acting formulation of ceftiofur, ceftiofur crystalline-free acid (CCFA), following SC injection to Asian elephants (Elephas maxim us).

Animals—11 adult Asian elephants.

Procedures—Each elephant received CCFA (6.6 mg/kg, SC) in the area caudoventral to the base of an ear. Blood samples were collected from an ear vein immediately prior to and at 0.5, 1, 2, 4, 8, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours after CCFA administration. Plasma concentrations of desfuroylceftiofur acetamide (the acetamide derivative of ceftiofur) were measured via ultrahigh-pressure liquid chromatography–tandem mass spectrometry. Data were analyzed via a noncompartmental pharmacokinetics approach.

Results—The mean ± SD maximum plasma concentration of desfuroylceftiofur acetamide was 1.36 ± 0.74 μg/mL and was detected at 4718 ± 31.30 hours. The mean ± SD area under the curve from time 0 to infinity was 2278 ± 55.8 μg•h/mL, and the mean residence time from time 0 to infinity was 158.2 ± 90.2 hours. The terminal elimination half-life associated with the slope of the terminal phase had a harmonic mean ± pseudo-SD of 83.36 ± 30.01 hours.

Conclusions and Clinical Relevance—Elephants tolerated CCFA at a dose of 6.6 mg/kg, SC, well. Dosing recommendations will depend on the mean inhibitory concentration of ceftiofur for each bacterial pathogen. Desfuroylceftiofur acetamide concentrations remained > 0.25 μg/mL for the entire 168-hour study period, which suggested CCFA would provide clinically relevant antimicrobial activity against certain pathogens for 7 to 10 days.

Contributor Notes

Dr. Adkesson's present address is Chicago Zoological Society, Brookfield Zoo, 3300 Golf Rd, Brookfield, IL 60513.

Dr. Allender's present address is Department of Comparative Biosciences, College of Veterinary Medicine, University of Illinois, Urbana, IL 61802.

Supported by the Saint Louis Zoo and Pfizer Inc.

The authors thank Dr. Mitch Finnegan, Martha Fischer, and Jim Naelitz for technical assistance and G. Scott Grover for assistance with the bioanalytic assays.

Address correspondence to Dr. Martín-Jiménez (tmartinj@utk.edu).