Fungal infections in vertebrates are usually opportunistic and occur with other diseases, in immunocompromised individuals and with physiological stressors.1,2 Terrestrial mammals are thought to be naturally resistant to fungal proliferation, in a healthy state, due to their endothermic nature as most fungi thrive in lower temperatures from 12–30 degrees Celsius (53.6–86 degrees Fahrenheit).2 Sea turtle body temperatures run lower due to their ectothermic thermoregulation and thus can potentially be an ideal host for pathogenic fungal infections. Fungal disease is a serious clinical concern in ill sea turtles affected by environmental stressors, trauma, overcrowding, and especially in cases of stranding where animals are typically hypothermic and debilitated. The management of fungal disease in sea turtles is important to their successful treatment. However, we have very few well-defined antifungal treatment protocols. The species of pathogenic fungi reported in sea turtles include but are not limited to Paecilomyces, Purpureocillium, Fusarium, Beauvaria, and Cladosporium. Susceptibility testing data available show that the azole antifungal agents itraconazole and voriconazole may be appropriate choices for antifungal therapy in sea turtles.4 We have selected to study voriconazole, a second-generation triazole antifungal drug, because of its’ broad-spectrum activity against Candida, Cryptococcus neoformans, Aspergillus, Fusarium, and many other dimorphic fungi.1,3,4 This study has three specific aims: (1) To determine the pharmacokinetic profile of single-dose voriconazole in green sea turtles (Chelonia mydas). (2) to evaluate the efficacy of the dose currently used by the authors and to assess this doses’ ability to reach therapeutic levels reported in other species.5,6 (3) to observe the treated animals for adverse effects since this has been observed in other animals.7,8 We hypothesize that the pharmacokinetic profile of voriconazole will allow us to develop a treatment regimen that will be safe and effective in most treated animals from our population, thus avoiding the requirement of expensive and inconvenient drug concentration monitoring that is required for human use.1,5,6 An initial pilot study was performed on three turtles. Results of this pilot study indicated that 5 mg/kg is likely too low and that a dose of 10 mg/kg voriconazole may be a more appropriate dose to reach therapeutic plasma levels. Interestingly, the results of the pilot study also indicated that an appropriate voriconazole dosing interval for turtles may be once to twice daily unlike other medications studied in this species which are often given at longer intervals.9 For the primary study, thirty-seven green sea turtles housed at SeaWorld California were included. All turtles were given a single oral dose of voriconazole at 10 milligrams per kilogram (mg/kg) (rounded to the nearest 50 mg). Blood samples were collected for plasma voriconazole concentration at time points T= 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 hours. Animals were pooled so that there were at minimum n=8 animals for each time point. Samples were sent to the Clinical Pharmacology Laboratory in the College of Veterinary Medicine of North Carolina State University for high-pressure liquid chromatography (HPLC) analysis for plasma drug concentration.
The authors would like to thank the veterinary technical and zoological support staff of SeaWorld San Diego for assistance with sampling for this study.
* Presenting author
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9. Innis CJ, Harms CA, Manire CA. 2017. Therapeutics. In: Manire CA, Norton TM, Stacy BA, Innis CJ, Harms CA, editors. Sea Turtle Health & Rehabilitation. Plantation, FL: J. Ross Publishing. p. 497–526.