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

Abstract

Simple Summary: Sharks and rays are a vital part of the collections of many aquariums around the world. The study of these species kept under human care has revealed a number of health conditions, highlighting the necessity of the further development of treatment plans. Although fungal infections are uncommon in elasmobranchs, they can lead to high mortality rates in aquariums. Some promising results have been reported with voriconazole, but pharmacokinetic studies are needed. In this study, voriconazole was administered IV and IM to six Nursehound sharks (Scyliorhinus stellaris) at a dose of 4 mg/kg, with blood samples subsequently collected for analysis. Pharmacokinetic analysis was carried out, and results showed a mean peak plasma concentration (Cmax) ± SEM of 3.00 ± 0.23 µg/mL following IM administration. Terminal half-lives for IV and IM injections were 7.94 ± 0.49 h and 4.27 ± 1.04 h, respectively. These results are promising; however, further susceptibility testing in elasmobranch fungal infections is necessary to evaluate the effectiveness of the posology proposed in this study..

Abstract: 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 (Scyliorhinus stellaris) (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 (Cmax) ± 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.