Introduction
Gilthead sea bream (Sparus aurata) farming is of great importance to European finfish mariculture accounting for 13% of its production value. A bottleneck to further increasing this species production is Sparicotyle chrysophrii, a gill-attaching blood-sucking monogenean, which is currently the most serious pathogen for gilthead seabream farming. To date, formalin bath treatments are the primary measure to battle sparicotylosis, however, bath applications in large cages are associated with several drawbacks.
Praziquantel (PZQ) is an anthelmintic drug widely used in veterinary medicine to control Platyhelminthes. The efficacy of the drug against a wide range of parasitic helminths in numerous farmed fish species has been recently reviewed (Bader et al. 2019; Norbury et al. 2022). Admittedly, drug pharmacokinetics (PKs) in the targeted organisms provide useful information optimizing treatment schedules. Nevertheless, to our knowledge, there is no literature examining the PKs of PZQ in gilthead seabream, thus, the present study attempts to investigate the kinetic profile and bioavailability (F) of dietary-administered PZQ in this species.
Materials and methods
Three hundred healthy gilthead seabream (52±3.7 g) were equally randomized in 3 groups of tanks; Low and High groups received an experimental diet supplemented with PZQ 75 mg/kg and 150 mg/kg, respectively, while the intravenous group received intravenously (i.v) the PZQ dosing of 75 mg/kg fish dissolved in DMSO (0.5 mL/kg BW). During the experimental procedure, fish were hand-fed once a day, assuring that the feed was consumed. Water temperature was maintained at 21±1°C. Ten fish/group were anesthetized (MS-222, 150 ppm) and blood samples were collected at 1, 2, 4, 6, 8, 12, 24, 48, 72, and 96 h post-treatment. Plasma was separated from blood by centrifugation (3000 g for 10 min at 4°C). Fish were then killed by an overdose of anaesthetic and gill samples were also collected. PZQ levels were analyzed after extraction by an HPLC-UV chromatographic apparatus.
Results and Discussion
Plasma PZQ concentrations after oral and i.v administration are shown in Figure 1. As expected, the double dosing resulted in significantly higher PZQ plasma levels although only an approximately 22% increase in Cmax (6.7 μg/mL for the low group vs 8.2 μg/mL for the high group) was observed. PZQ elimination from fish circulation following dietary administrations was found to be relatively sharp for both examined dosing regimens albeit distinguished profiles were evident. Particularly, the elimination half-life (t1/2β) was shorter at high compared to the low PZQ dosing, revealing values of 14.4 and 25.7 h, respectively. The F of PZQ was calculated to be 49%, confirming a high absorption in fish circulation. In agreement with this, a high F of PZQ (51%) has also been reported in yellowtail kingfish (S. lalandi) (Tubbs & Tingle 2006).
Gill PZQ concentrations in gilthead seabream after two single oral doses are shown in Figure 2. The maximum concentrations of PZQ in fish fed 75 and 150 mg/kg were found 20.7 and 39.1 μg/g, respectively, 4 h post-feeding. Additionally, a dose-dependent effect in relative exposure to PZQ was observed. Furthermore, the t1/2β of PZQ in fish fed the low dose was found at 8.9 h while in the high-dose group, the corresponding value was calculated to be 11.7 h, indicating faster elimination for the low dosing. The aforementioned results clearly indicate that among examined tissues, distinct kinetic profiles of PZQ exist. Since a route of xenobiotics elimination may be via the gills (Hansen et al. 2001), the discrepancies in drug PKs between plasma and gills found herein could be attributed to this assumption.
Conclusions
Based on the information obtained from the PZQ analysis in the gilthead seabream body compartment, the 150 mg/kg dosing regimen is superior to the 75 mg/kg, as confirmed by the significantly higher drug levels in all tested tissues. Since PZQ concentration trends to decrease sharply and the elimination time of the drug in plasma was shorter in fish that received the 150 mg/kg dosing regimen, the daily dosing should be divided into two medicated meals, to ensure adequate drug circulatory levels during treatments. The efficacy of the proposed medicated scheme remains to be evaluated in field trials against S. chrysophrii.
Acknowledgment
The project is co-funded by Greece and the European Union under the Fisheries and Maritime Operational Program 2014-2020 (75% EMFF contribution, 25% National Contribution). https://praziquantel.gr/
References
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Tubbs LA, Tingle MD (2006) Bioavailability and pharmacokinetics of a praziquantel bolus in kingfish Seriola lalandi. Diseases of Aquatic Organisms, 69, 233-238.
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