Oral Presentation 64th International Conference of the Wildlife Disease Association 2015

A pharmacokinetic investigation of florfenicol as a possible treatment of chlamydial disease in koalas (Phascolarctos cinereus) (#32)

Christie Budd 1 , Merran Govendir 1 , Amber Gillett 2
  1. Faculty of Veterinary Science, University of Sydney, Camperdown, NSW, Australia
  2. Australia Zoo Wildlife Hospital, Australia Zoo, Beerwah, QLD, Australia

Background

Florfenicol is being investigated as an alternate treatment of chlamydiosis in koalas. Systemic chlamydiosis is the most important infectious disease of koalas, causing significant morbidity, mortality and infertility(1). Chloramphenicol base suspension is reportedly the most effective treatment, (2) but this formulation was unavailable at the commencement of these trials.

Hypotheses

1. Florfenicol will be effectively absorbed and provide theoretically therapeutic plasma concentrations in koalas following subcutaneous administration.

2. Florfenicol will represent a convenient and effective alternative to chloramphenicol for the treatment of chlamydial disease in koalas.

Materials and Methods

A new sample handling method has been developed to remove interfering endogenous compounds in koala plasma to produce a florfenicol assay utilizing High Performance Liquid Chromatography. 

Florfenicol (Nuflor, MSD) has been administered to koalas with naturally occurring chlamydiosis. Blood samples were taken at serial time points following subcutaneous (SC) and intravenous (IV) administration for pharmacokinetic analysis.  

Results

Poor absorption was noted following a single subcutaneous injection. The mean maximum concentration (Cmax) of florfenicol in plasma of 3 koalas given 20 mg/kg SC was 1.2 μg/ml, attained 4 hours after administration. Following intravenous administration at 10mg/kg, the mean (n=3) florfenicol concentration at 24 hours post treatment was 25μg/mL.

Conclusions

A therapeutic target of 1-2μg/mL in plasma has been established based on the minimum drug concentration necessary to inhibit Chlamydia pecorum growth in vitro.(3).

Florfenicol at a dose of 20mg/kg SC is unlikely to be useful in treating koalas with chlamydiosis. Field data suggests that koalas will not tolerate higher SC doses. Intravenous administration of florfenicol may well prove efficacious, however caution must be taken with administering florfenicol via this route as an anaphylactoid reaction has been observed in one koala.

References

  1. Polkinghorne, Adam, Jon Hanger and Peter Timms. "Recent Advances in Understanding the Biology, Epidemiology and Control of Chlamydial Infections in Koalas." Veterinary Microbiology 165, no. 3-4 (2013): 214-223.
  2. Govendir, M., J. Hanger, J. J. Loader, B. Kimble, J. E. Griffith, L. A. Black, M. B. Krockenberger and D. P. Higgins. "Plasma Concentrations of Chloramphenicol after Subcutaneous Administration to Koalas ( Phascolarctos Cinereus) with Chlamydiosis." Journal of Veterinary Pharmacology and Therapeutics 35, no. 2 (2012): 147-154.
  3. Black, L. A. "Aspects of the Pharmacokinetics and Pharmacodynamics of Chloramphenicol, Enrofloxacin and Fluconazole in Koalas (Phascolarctos Cinereus)." PhD thesis, University of Sydney, 2013