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在条纹斑竹鲨(Scyliorhinus stellaris)和波状鳐(Raja undulata)中以50毫克/千克口服伏立康唑的药代动力学研究。

Pharmacokinetic study of voriconazole administered orally at 50 mg/kg in nursehound sharks (Scyliorhinus stellaris) and udulate skates (Raja undulata).

作者信息

Cañizares-Cooz Daniela, García-Párraga Daniel, Álvaro-Álvarez Teresa, Rubio-Langre Sonia, Encinas Teresa, Morón-Elorza Pablo

机构信息

Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Complutense University of Madrid, Av. Puerta de Hierro s/n, Madrid, 28040, Spain.

Fundación Oceanogràfic de la Comunitat Valenciana, Ciudad de las Artes y las Ciencias, C/ Eduardo Primo Yúfera (Científic) 1B, Valencia, 46013, Spain.

出版信息

BMC Vet Res. 2025 Jul 23;21(1):484. doi: 10.1186/s12917-025-04930-6.

Abstract

BACKGROUND

Fungal diseases represent an ongoing problem for elasmobranchs kept under human care worldwide. When present, mycoses often lead to high mortality rates, compromising welfare and conservation programs in aquariums. Various fungal species have been identified as causative agents, with Fusarium solani complex most frequently being isolated. Treatment remains unclear; however, recent clinical reports have shown positive outcomes after the administration of azole antifungal drugs to elasmobranchs affected by different fungal infections, specifically for voriconazole. Clinical cases report different dose regimens and administration routes, and pharmacokinetic (PK) studies in elasmobranchs are needed. For this purpose, a PK study was performed and voriconazole was administered at 50 mg/kg PO to six nursehound sharks (Scyliorhinus stellaris) and six undulate skates (Raja undulata). Plasma concentrations were determined using a validated high-performance liquid chromatography (HPLC) method, and PK parameters were estimated using a non-compartmental model.

RESULTS

The mean peak plasma concentration (C) ± standard error of the mean (SEM) after oral administration of 50 mg/kg of voriconazole was 3.32 ± 0.92 µg/ml in nursehound sharks and 10.53 ± 0.91 µg/ml in undulate skates. Terminal-half lives for sharks and skates resulted 113.43 ± 29.45 h and 9.88 ± 1.33 h, respectively. Plasma concentrations were above MIC in vitro values for Fusarium solani for 54 to 72 h.

CONCLUSIONS

These findings suggest that voriconazole persists longer in sharks due to extended half-life, whereas in skates, the drug reaches higher plasma concentrations but is eliminated more rapidly. These interspecies variations should be considered when selecting the oral administration route for treatment and determining the appropriate posology regimens for antifungal therapy in elasmobranchs.

摘要

背景

真菌病是全球人工饲养的板鳃亚纲动物面临的一个持续存在的问题。真菌病一旦出现,往往会导致高死亡率,影响水族馆的动物福利和保护计划。已确定多种真菌为病原体,其中茄病镰刀菌复合体最为常见。治疗方法尚不明确;然而,最近的临床报告显示,对受不同真菌感染的板鳃亚纲动物使用唑类抗真菌药物后取得了积极效果,特别是伏立康唑。临床病例报告了不同的剂量方案和给药途径,因此需要对板鳃亚纲动物进行药代动力学(PK)研究。为此,进行了一项PK研究,对6条姥鲨(Scyliorhinus stellaris)和6条波状鳐(Raja undulata)口服给予50mg/kg的伏立康唑。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计PK参数。

结果

口服50mg/kg伏立康唑后,姥鲨的平均血浆峰浓度(C)±平均标准误差(SEM)为3.32±0.92μg/ml,波状鳐为10.53±0.91μg/ml。鲨鱼和鳐的终末半衰期分别为113.43±29.45小时和9.88±1.33小时。血浆浓度在体外对茄病镰刀菌的最低抑菌浓度(MIC)以上持续54至72小时。

结论

这些发现表明,由于半衰期延长,伏立康唑在鲨鱼体内持续时间更长,而在鳐体内,药物达到更高的血浆浓度,但消除更快。在选择口服给药途径进行治疗以及确定板鳃亚纲动物抗真菌治疗的合适剂量方案时,应考虑这些种间差异。

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