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

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 (Cmax) ± 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 MIC50 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