Cañizares-Cooz Daniela, García-Párraga Daniel, Rubio-Langre Sonia, Encinas Teresa, Morón-Elorza Pablo
Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Complutense University of Madrid, Av. Puerta de Hierro s/n, 28040 Madrid, Spain.
Fundación Oceanogràfic de la Comunitat Valenciana, C/Eduardo Primo Yúfera (Científic), 1B, 46013 Valencia, Spain.
Vet Sci. 2025 Jan 3;12(1):17. doi: 10.3390/vetsci12010017.
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.
真菌病尽管在鲨鱼和鳐类中的发病率较低，但在这类动物中被视为新兴疾病，即便经过治疗也可能导致高死亡率。与板鳃亚纲动物真菌病治疗相关的现有信息有限，且常常基于与这些物种打交道的专业人员和临床医生提供的经验知识。使用唑类抗真菌药物，尤其是伏立康唑，已显示出有望成为板鳃亚纲动物真菌感染的潜在治疗选择，在一些已记录病例中取得了良好效果。然而，关于鱼类中唑类药物药代动力学（PK）的科学知识仍然有限，尽管最近发表了一项关于伏立康唑在鳐类中的PK研究，但仍没有关于鲨鱼中唑类药物的PK研究发表。在本研究中，以4毫克/千克的剂量对姥鲨（）静脉内（IV）和肌肉内（IM）注射伏立康唑（n = 6）。在给药前以及给药后的九个预定时间间隔（0.25、0.5、1、1.5、2、4、8、12、24和36小时）采集血样。使用经过验证的高效液相色谱（HPLC）方法测定血浆浓度，并使用非房室模型估算药代动力学（PK）参数。肌肉注射后平均血浆峰浓度（C）±SEM为3.00±0.23微克/毫升。静脉注射和肌肉注射后的分布容积（Vd）分别为1.39±0.09升/千克和1.50±0.18升/千克，两条给药途径之间无统计学显著差异。静脉注射后的清除率（Cl）值为0.12±0.01毫升/分钟，肌肉注射后的清除率为0.29±0.05毫升/分钟。在研究期间或给药后四周未检测到不良反应。这些结果支持在鲨鱼中静脉注射和肌肉注射伏立康唑；然而，有必要进行更多关于毒性和药效学的研究。此外，需要进一步研究影响板鳃亚纲动物的真菌病原体的易感性，以确定肌肉注射伏立康唑治疗鲨鱼真菌病的最佳给药方案。
