Abstract

The pharmacokinetics of the antifungal drug, fluconazole, were studied in juvenile loggerhead sea turtles (Caretta caretta) following single i.v. and s.c. injections. Using parameters determined in the single dose study, a multiple-dose s.c. regimen was then derived and tested.

Pharmacokinetic parameters were calculated, using a two-compartment model, from plasma concentration-time data obtained following single i.v. and s.c. administrations of fluconazole at a dose of 2.5 mg/kg body weight in six juvenile sea turtles, using a cross-over study design. Blood samples were collected at intervals for 120 hours following each single dose. Plasma fluconazole concentrations were measured by reverse-phase high performance liquid chromatography. The i.v. and s.c. elimination half-lives were (mean +/- s.d.) 139.5 +/- 36.0 hours and 132.6 +/- 48.7 hours respectively. Systemic clearance of fluconazole was 8.2 +/- 4.3 ml/hr/kg and the apparent volume of distribution was 1.38 +/- 0.29 L/kg. Systemic absorption of fluconazole after s.c. administration was complete. The derived multiple-dose regimen consisted of a loading dose of 21 mg/kg body weight and subsequent doses of 10 mg/kg administered via s.c. injection every 120 hours (5 days). This regimen was administered to four juvenile sea turtles for 10 days and blood samples were taken to obtain peak and trough plasma concentrations of fluconazole. Mean peak concentrations were 16.9 +/- 1.1 µg/ml 4 hours after the loading dose, and 19.1 +/- 2.8 µg/ml 4 hours after the third dose. Mean trough concentrations were 7.2 +/- 2.2 µg/ml 5 days after the first dose, 10.4 +/- 2.7 µg/ml 5 days after the second dose, and 10.7 +/- 2.9 µg/ml 5 days after the third dose. The terminal half-life was calculated at 143 hours.

Throughout multiple dosing, fluconazole concentrations remained near or above 8 µg/ml, a trough concentration of fluconazole targeted when treating human mycotic infections similar to · fungal pathogens of sea turtles. Results of this study suggest that fluconazole can be effectively administered to sea turtles at a dose of 10 mg/kg body weight every 5 days following a loading dose of 21 mg/kg.

Acknowledgements

This work was supported by the North Carolina Veterinary Medical Foundation and the Office of the Dean for Research, North Carolina State University, College of Veterinary Medicine. We thank Jay Barnes and the North Carolina Aquarium at Pine Knoll Shores, Jean Beasley and the Karen Beasley Sea Turtle Rescue and Rehabilitation Center, Ruth Boettcher and the North Carolina Wildlife Resources Commission, Cristy Bleck, Elizabeth Chittick, Adrien Elliott, Bob Jones, Stuart May, Jeff McBane, Kristy McNeal, Delta Plummer, and Rick Schultz for their help in this study.