In vitro binding of cefovecin to plasma proteins in Australian marsupials and plasma concentrations of cefovecin following single subcutaneous administration to koalas (Phascolarctos cinereus)

Aust Vet J. 2019 Mar;97(3):75-80. doi: 10.1111/avj.12785.

Abstract

Background: Cefovecin has a long duration of antibiotic activity in cats and dogs, somewhat attributable to its high plasma protein binding.

Aims: To determine the cefovecin binding to plasma proteins in vitro in selected Australian marsupials and to quantify the change in cetovecin concentration over time following subcutaneous injection in koalas.

Methods and results: Various cefovecin concentrations were incubated with plasma and quantified using HPLC. The median (range) bound percentages when 10 μg/mL of cefovecin was incubated with plasma were 11.1 (4.1-20.4) in the plasma of the Tasmanian devil, 12.7 (5.8-17.3) in the koala, 18.9 (14.6-38.0) in the eastern grey kangaroo, 16.9 (15.7-30.2) in the common brush-tailed possum, 37.6 (25.3-42.3) in the eastern ring-tailed possum and 36.4 (35.0-38.3) in the red kangaroo, suggesting that cefovecin may have a shorter duration of action in these species than in cats and dogs. Cefovecin binding to plasma proteins in thawed, frozen equine plasma was also undertaken for assay quality control and the median (range) plasma protein binding (at 10 μg/mL) was 95.6% (94.9-96.6%). Cefovecin was also administered to six koalas at 8 mg/kg subcutaneously and serial blood samples were collected at 3, 6, 24, 48, 72, 96 h thereafter. Cefovecin plasma concentrations were not quantifiable in four koalas and in the other two, the mean plasma concentration at t = 3 h was 1.04 ± 0.01 μg/mL.

Conclusion: Because of the limited pharmacokinetic data generated, no further pharmacokinetic analysis was performed; however, a single injected bolus of cefovecin is likely to have a short duration of action in koalas (hours, rather than days).

Keywords: cephalosporin; high-performance liquid chromatography; koalas; marsupials; plasma protein binding.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / metabolism*
  • Anti-Bacterial Agents / pharmacokinetics
  • Australia
  • Blood Proteins / metabolism*
  • Cephalosporins / administration & dosage
  • Cephalosporins / metabolism*
  • Cephalosporins / pharmacokinetics
  • Chromatography, High Pressure Liquid / veterinary
  • Female
  • In Vitro Techniques
  • Injections, Subcutaneous / veterinary
  • Male
  • Marsupialia / blood*
  • Marsupialia / metabolism
  • Phascolarctidae / blood
  • Phascolarctidae / metabolism

Substances

  • Anti-Bacterial Agents
  • Blood Proteins
  • Cephalosporins
  • cefovecin