Voriconazole Pharmacokinetics Administered at 4 mg/kg IM and IV in Nursehound Sharks () Under Human Care.

Fungal diseases, despite their low incidence in sharks and rays, are considered emerging diseases in this group of animals and can lead to high mortality rates despite treatment. The information available related to the treatment of fungal diseases in elasmobranchs is limited and is frequently based on the empirical knowledge provided by the professionals and clinicians working with these species. The use of azole antifungal drugs, especially voriconazole, has shown promise as a potential treatment option for fungal infections in elasmobranchs, with favorable outcomes in some registered cases. However, scientific knowledge regarding azole pharmacokinetics (PK) in fish remains limited, and despite the recent publication of a PK study with voriconazole in rays, there are still no published PK studies for azoles in sharks. In this study, voriconazole was administered at 4 mg/kg intravenously (IV) and intramuscularly (IM) to nursehound sharks () (n = 6). Blood samples were collected before administration and at nine predetermined time intervals afterwards (0.25, 0.5, 1, 1.5, 2, 4,8,12, 24, and 36 h). Plasma concentrations were determined using a validated high-performance liquid chromatography (HPLC) method, and pharmacokinetic (PK) parameters were estimated using a non-compartmental model. The mean peak plasma concentrations (C) ± SEM after IM administration was 3.00 ± 0.23 µg/mL. The volume of distribution (Vd) after IV and IM administration resulted in 1.39 ± 0.09 L/kg and 1.50 ± 0.18 L/kg, respectively, showing no statistically significant differences between the two routes. Clearance (Cl) values were 0.12 ± 0.01 mL/min after IV administration and 0.29 ± 0.05 mL/min after IM administration. No adverse effects were detected during the study or four weeks after administration. These results support the administration of IV and IM voriconazole in sharks; however, additional studies on toxicity and pharmacodynamics are necessary. Moreover, further research on the susceptibility of fungal pathogens affecting elasmobranchs is needed to establish an optimal dosing regimen for IM voriconazole in the treatment of mycosis in sharks.