Kanwal J. Varma

Single dose pharmacokinetic study of florfenicol in Atlantic salmon (Salmo salar) in seawater at 11°C

Abstract The pharmacokinetics of intravenously and orally administered florfenicol were determined in Atlantic salmon (Salmo salar) weighing 194±40 g (mean±s.d.). The study was performed at 10.8±1.5°C. A dose of 10 mg florfenicol/kg body weight was administered either intravenously or orally to groups of 85 fish each. At seven time points, from 3 h to 120 h after administration, blood was sampled from 10 individual fish in each group. The plasma was assayed for florfenicol using an HPLC method. The pharmacokinetic modelling of the results was performed using the computer program PCNONLIN. Following intravenous administration, the plasma concentration-time data of florfenicol were best described by a two-compartment open model. The volume of distribution at steady state, Vd(ss), and the total body clearance, ClT, were 1.122 l/kg and 0.086 l/h·kg, respectively. The elimination halflife, t 1 2 β , was estimated as 12.2 h. Following oral administration, the plasma concentration-time data of florfenicol were best described by a one-compartment open model with first order absorption and elimination. Peak plasma concentration, Cmax, was estimated at 4.0 μg/ml and was estimated to occur at 10.3 h (Tmax) following dosing. The bioavailability, F, was estimated at 96.5%. Based on the median minimum inhibitory concentrations (MICs) of 0.8 μg/ml reported for Aeromonas salmonicida, Vibrio anguillarum and Vibrio salmonicida, plasma concentrations should remain above the MIC for 36–40 h following a single oral dose of 10 mg florfenicol/kg.

Field trials to evaluate the efficacy of emamectin benzoate in the control of sea lice, Lepeophtheirus salmonis (Krøyer) and Caligus elongatus Nordmann, infestations in Atlantic salmon Salmo salar L.

Abstract Three field trials were conducted to evaluate the efficacy of emamectin benzoate as a treatment for sea lice, Lepeophtheirus salmonis (Kroyer) and Caligus elongatus (Nordmann), infestations on Atlantic salmon Salmo salar (L.). Trials were carried out at sea temperatures of 13.0–15.5°C and 7.2–8.5°C. Salmon naturally infested with sea lice, with mean weights of 438, 513 and 2662 g, respectively, were held in experimental pens on commercial sites. At day −1 or −2, 20 or 30 fish were sampled from each pen to determine pre-treatment numbers of lice. Emamectin benzoate was administered in-feed at a dose of 50 μg kg −1 biomass day −1 for 7 consecutive days. Sea lice were counted again on days 7, 14 and 21, and comparisons made with untreated control fish. Treatment with emamectin benzoate was effective against chalimus and motile stages of sea lice. In all three trials, treated groups were surrounded by pens of heavily infested fish and L. salmonis numbers increased over time on control fish by 87–284%, whereas over the same period, L. salmonis were reduced on treated fish by 68–98%. In the low temperature trial, reductions were slower but numbers were still 90% lower than on control fish at day 21. At the end of the third trial, both control pens were treated with hydrogen peroxide owing to heavy lice burdens. However, L. salmonis numbers rapidly increased again and at day 55, fish treated only with emamectin benzoate still had 80% fewer lice than control fish. In the two summer trials, large numbers of C. elongatus were rapidly reduced by treatment with 82–84% efficacy by day 21. Despite the potential for continuous re-infestation, oral treatment with emamectin benzoate presented an effective means of controlling all parasitic stages of L. salmonis and C. elongatus on farmed salmon, and in one trial, numbers remained lower on treated fish for at least 55 days.

The disposition of 14C-florfenicol in Atlantic salmon (Salmo salar)

Abstract The absorption, distribution, metabolism and excretion of 14C-labelled florfenicol in Atlantic salmon held in sea water at 8.5–11.5°C were studied by means of whole body autoradiography (WBA), liquid scintillation counting (LSC) and high performance liquid chromatography (HPLC). Uniformly ring-labelled 14C-florfenicol was mixed in capelin oil, and coated on ordinary fish feed. Each of 28 fish (139.6±18.4 g) was gavaged with a single dose of 10 mg/kg bodyweight of florfenicol, corresponding to 119.05 μCi/kg bodyweight. Whole fish were sampled from 3 h to 56 days after administration, and were analyzed by WBA and LSC. Muscle samples from fish sampled 6 h to 3 days after administration were analysed by HPLC, and LSC of fractions of the eluate. Peak radioactivity levels were detected in most tissues at 12 h after administration (3 days in the kidney), and declined thereafter. The radioactivity in the brain was low compared with that in muscle and blood, suggesting that the passage of the blood-brain barrier by florfenicol or its metabolites is limited. Radioactivity levels in blood and muscle were similar at all times. Accumulation of radioactivity could be seen in the kidney and the choroidea of the eye, indicating a possible affinity to melanin. The radioactivity was excreted both via urine and bile. There were trace amounts of radioactivity in skin, liver and kidney tissues of fish sampled 56 days post administration, while no radioactivity was detected in any blood or muscle samples taken later than 28 days after administration. The fraction of parent florfenicol in muscle decreased from approximately 90% (6 h) to about 20% (3 days), while the fraction of florfenicol amine increased from about 7% to about 70% during the same period. Other metabolites were detected, but were quantitatively of minor importance. The results strongly suggest that florfenicol is rapidly metabolized in the body of Atlantic salmon, and that the dominant metabolite is florfenicol amine.

Tolerance of Atlantic salmon, Salmo salar L., and rainbow trout, Oncorhynchus mykiss (Walbaum), to emamectin benzoate, a new orally administered treatment for sea lice

Abstract Atlantic salmon (weight range 289–484 g) and rainbow trout (weight range 166–387 g), held in seawater, were fed medicated diets containing graded levels of emamectin benzoate for 7 days. Nominal dose rates were 0, 100, 250 and 500 μg kg−1 body weight day−1 (equivalent to 0, 2, 5 and 10 times recommended dose rate for treatment of sea lice). Fish were observed for a further 7 days to determine the effects of treatment. Calculated actual dose rates, compensated for feed concentrations determined by chemical analysis, feed intake and weight gain during the course of the study, were 0, 70, 173 and 356 μg kg−1 body weight day−1 for Atlantic salmon, and 0, 88, 218 and 413 μg kg−1 body weight day−1 for rainbow trout. No mortality was observed, which could be related to treatment and unequivocal signs of toxicity were recorded only at the highest dose used in these studies. Signs of emamectin benzoate toxicity in both species included lethargy, dark coloration and inappetance. Atlantic salmon also showed loss of coordination. Fish in the high-dose groups exhibiting signs of toxicity showed no evidence of recovery during the 7-day post-treatment period. No pathognomonic signs of emamectin benzoate toxicity were identified during gross necropsy or histopathological examination.