Abstract

Keeping and breeding of tropical fishes is a popular hobby throughout the world. Many sick fish are treated by aquaculturists, hobbyists, and pet store clerks with chemotherapeutants which have been purchased over the counter. There is a need for sound pharmacokinetic data in ornamental fish on antimicrobials that are available to the practicing veterinarian.

The red pacu was selected because it is relatively large, hardy, popular in the hobby, and belongs in the characin order. This taxonomic group contains many economically important tropical fishes including the hundreds of species of tetras, silver dollars, headstanders, and hatchetfishes. Pacu are also cultured for food in several Latin American countries.

Florfenicol is a structural analogue of chloramphenicol similar to thiamphenicol, but with more activity against some organisms than chloramphenicol. It differs importantly from chloramphenicol in that it lacks the para-nitro group that is believed to be responsible for the problems of aplastic anemia.¹ However, dose-related hematologic changes are also a potential problem with florfenicol, as they are with chloramphenicol.²

Florfenicol works by inhibiting bacterial protein synthesis at the ribosome.³ Florfenicol activity against bacteria differs from chloramphenicol because florfenicol is not susceptible to the same resistance mechanisms as chloramphenicol. Organisms resistant to chloramphenicol may still be susceptible to florfenicol. Florfenicol has been demonstrated to be efficacious against bacteria of fish, especially salmonids.^4-9 Florfenicol has been proven to be clinically effective in controlling a variety of bacterial diseases in salmonids and is approved for use in Europe and Asia.

Florfenicol has been administered orally for treatment of infections in captive fish in Europe under the trade name, Aquafen®. In rainbow trout (Oncorhynchus mykiss) kept at 10°C, an oral dose of 10 mg/kg had a mean residence time of 21 hours and a C_MAX of 3.23 mcg/ml.¹⁰ Pharmacokinetics have also been described for Atlantic salmon, Salmo salar.¹¹ Because chloramphenicol pharmacokinetics vary among animal species, a similar pattern was expected for florfenicol.¹² This study was conducted since species specific pharmacokinetic information is needed to ensure accurate dosing and to avoid toxicity.

The objectives of this study were to determine the maximum serum concentrations, elimination half-life, and relative bioavailability of florfenicol in the red pacu following single dose intramuscular administration. Results of this research can be compared with existing information on the clinical efficacy of this drug and will provide a foundation for determining intramuscular treatment protocols for florfenicol in ornamental fishes. This data can be correlated with in-vitro minimum inhibitory concentration (MIC) for given bacterial pathogens in order to design safe and effective clinical treatment protocols.

The intramuscular (IM) disposition of florfenicol was evaluated following a single dose administration to a cultured population of twelve red pacu. The mean half-life, Vd/F, and Cl/F was 4.25 hours, 5.69 L/kg, and 0.92 L/kg/hour, respectively. The 3 hour C_MAX of 1.09 (+/-0.12) mcg/ml following a single 10.0 mg/kg dosing was consistent with in-vitro MIC data for Aeromonas salmonicida and Vibrio salmonicida. These data show that florfenicol was eliminated rapidly and had a large volume of distribution when injected IM in pacu at a dose of 10 mg/kg. Considering that susceptible bacteria would have an MIC 1.25 mcg/ml (NCCLS), and if plasma concentrations are maintained in this range throughout the dosing interval, an estimated dose of 20-30 mg/kg administered IM every 24 hours would be required. Chronic dosing studies are needed to determine the accuracy of this dose estimation.

Acknowledgements

The authors thank Delta Plummer for assistance with sample analysis and Jessica Geyer for assisting with fish maintenance. This study was supported by the state of North Carolina.

References

1.  Manyan DR, Arimura GK, AA Yunis. 1975. Comparative metabolic effects of chloramphenicol analogues. Molec. Pharm. 11(5):520-527.

2.  Yunis AA. 1988. Chloramphenicol: relation of structure to activity and toxicity. Annu. Rev. Pharmacol. Toxicol. 28:83-100.

3.  Cannon M, Jarford S, J Davies. 1990. A comparative study on the inhibitory actions of chloramphenicol, thiamphenicol and some fluorinated analogs. Journal of Antimicrobial Chemotherapy 18:311-316.

4.  Fukui H, Fujihara Y, T Kano. 1987. In vitro and in vivo antibacterial activities of florfenicol, a new fluorinated analog of thiamphenicol, against fish pathogens. Fish Pathol. 22:201-207.

5.  Inglis V, RH Richards. 1991. The in vitro susceptibility of Aeromonas salmonicida and other fish pathogenic bacteria to 29 antimicrobial agents. J of Fish Diseases 14:641-650.

6.  Nordmo R, Varma KJ, Sutherland IH, ES Brokken. 1994. Florfenicol in Atlantic salmon, Salmo salar L.: field evaluation of efficacy against furunculosis in Norway. J of Fish Diseases 17:239-244.

7.  Inglis V, Richards RH, Varma KJ, Sutherland I, ES Brokken. 1991. Florfenicol in Atlantic salmon, Salmo salar L., parr: tolerance and assessment of efficacy against furunculosis. J of Fish Diseases, 14:343-351.

8.  Nordmo R, Riseth JMH, Varma KJ, Sutherland IH, ES Brokken. 1998. Evaluation of florfenicol in Atlantic salmon, Salmo salar L.: efficacy against furunculosis due to Aeromonas salmonicida and cold water vibriosis due to Vibrio salmonicida. J of Fish Diseases 21:289-297.

9.  Samuelsen OB, Hjeltnes B, J Glette. 1998. Efficacy of orally administered florfenicol in the treatment of furunculosis in Atlantic salmon. Journal of Aquatic Animal Health 10:56-61.

10. Pinault LP, Millot LK, PJ Sanders. 1997. Absolute oral bioavailability and residues of florfenicol in the rainbow trout (Oncorhynchus mykiss). J. Vet Pharmacol. Therap 20(Suppl. 1), 297-298.

11. Martinsen B, Horsberg TE, Varma KJ, R Sams. 1993. Single dose pharmacokinetic study of florfenicol in Atlantic salmon (Salmo salar) in seawater at 11°C. Aquaculture 112:1-11.

12. Davis L, Neff CA, Baggot JD, TE Powers. 1972. Pharmacokinetics of chloramphenicol in domestic animals. Am. J. of Vet. Res 33:2259-2266.