Voriconazole Pharmacokinetics Administered at 4 mg/kg IM and IV in Nursehound Sharks (<i>Scyliorhinus stellaris</i>) 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...

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Main Authors: Daniela Cañizares-Cooz, Daniel García-Párraga, Sonia Rubio-Langre, Teresa Encinas, Pablo Morón-Elorza
Format: Article
Language:English
Published: MDPI AG 2025-01-01
Series:Veterinary Sciences
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Online Access:https://www.mdpi.com/2306-7381/12/1/17
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author Daniela Cañizares-Cooz
Daniel García-Párraga
Sonia Rubio-Langre
Teresa Encinas
Pablo Morón-Elorza
author_facet Daniela Cañizares-Cooz
Daniel García-Párraga
Sonia Rubio-Langre
Teresa Encinas
Pablo Morón-Elorza
author_sort Daniela Cañizares-Cooz
collection DOAJ
description 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 (<i>Scyliorhinus stellaris</i>) (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<sub>max</sub>) ± 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.
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spelling doaj-art-aaca99e54bc14d84917fc8900ee094ba2025-01-24T13:52:00ZengMDPI AGVeterinary Sciences2306-73812025-01-011211710.3390/vetsci12010017Voriconazole Pharmacokinetics Administered at 4 mg/kg IM and IV in Nursehound Sharks (<i>Scyliorhinus stellaris</i>) Under Human CareDaniela Cañizares-Cooz0Daniel García-Párraga1Sonia Rubio-Langre2Teresa Encinas3Pablo Morón-Elorza4Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Complutense University of Madrid, Av. Puerta de Hierro s/n, 28040 Madrid, SpainFundación Oceanogràfic de la Comunitat Valenciana, C/Eduardo Primo Yúfera (Científic), 1B, 46013 Valencia, SpainDepartment of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Complutense University of Madrid, Av. Puerta de Hierro s/n, 28040 Madrid, SpainDepartment of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Complutense University of Madrid, Av. Puerta de Hierro s/n, 28040 Madrid, SpainDepartment of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Complutense University of Madrid, Av. Puerta de Hierro s/n, 28040 Madrid, SpainFungal 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 (<i>Scyliorhinus stellaris</i>) (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<sub>max</sub>) ± 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.https://www.mdpi.com/2306-7381/12/1/17sharksmycosisvoriconazolepharmacology
spellingShingle Daniela Cañizares-Cooz
Daniel García-Párraga
Sonia Rubio-Langre
Teresa Encinas
Pablo Morón-Elorza
Voriconazole Pharmacokinetics Administered at 4 mg/kg IM and IV in Nursehound Sharks (<i>Scyliorhinus stellaris</i>) Under Human Care
Veterinary Sciences
sharks
mycosis
voriconazole
pharmacology
title Voriconazole Pharmacokinetics Administered at 4 mg/kg IM and IV in Nursehound Sharks (<i>Scyliorhinus stellaris</i>) Under Human Care
title_full Voriconazole Pharmacokinetics Administered at 4 mg/kg IM and IV in Nursehound Sharks (<i>Scyliorhinus stellaris</i>) Under Human Care
title_fullStr Voriconazole Pharmacokinetics Administered at 4 mg/kg IM and IV in Nursehound Sharks (<i>Scyliorhinus stellaris</i>) Under Human Care
title_full_unstemmed Voriconazole Pharmacokinetics Administered at 4 mg/kg IM and IV in Nursehound Sharks (<i>Scyliorhinus stellaris</i>) Under Human Care
title_short Voriconazole Pharmacokinetics Administered at 4 mg/kg IM and IV in Nursehound Sharks (<i>Scyliorhinus stellaris</i>) Under Human Care
title_sort voriconazole pharmacokinetics administered at 4 mg kg im and iv in nursehound sharks i scyliorhinus stellaris i under human care
topic sharks
mycosis
voriconazole
pharmacology
url https://www.mdpi.com/2306-7381/12/1/17
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