Salmon lice, Lepeophtheirus salmonis, are naturally occurring parasites of salmon in sea water. Intensive salmon farming provides better conditions for parasite growth and transmission compared with natural conditions, creating problems for both the salmon farming industry and, under certain conditions, wild salmonids. Salmon lice originating from farms negatively impact wild stocks of salmonids, although the extent of the impact is a matter of debate. Estimates from Ireland and Norway indicate an odds ratio of 1.1:1-1.2:1 for sea lice treated Atlantic salmon smolt to survive sea migration compared to untreated smolts. This is considered to have a moderate population regulatory effect. The development of resistance against drugs most commonly used to treat salmon lice is a serious concern for both wild and farmed fish. Several large initiatives have been taken to encourage the development of new strategies, such as vaccines and novel drugs, for the treatment or removal of salmon lice from farmed fish. The newly sequenced salmon louse genome will be an important tool in this work. The use of cleaner fish has emerged as a robust method for controlling salmon lice, and aquaculture production of wrasse is important towards this aim. Salmon lice have large economic consequences for the salmon industry, both as direct costs for the prevention and treatment, but also indirectly through negative public opinion.
In contrast to mammalian therapeutics, the use of pharmaceutical substances is rather limited in fish. It is basically restricted to anaesthetic agents and anti-infective agents for parasitic and microbial diseases. Anaesthetic agents are used primarily in fish farm and laboratory settings to provide analgesia and immobilization of fish for minor procedures. The anti-infective agents are used for controlling diseases and the choice of drug depends on efficacy, ease of application, human safety, target animal safety including stress to the fish, environmental impact, regulatory approval, costs, and implications for marketing the fish. In this article, the major drugs used in salmonids in North America and Europe will be reviewed and some insight into future directions for drug development and use for the salmonid industry will be introduced. The mechanisms of action, pharmacokinetics, side effects, and uses of the drugs are emphasized.
In Northern Europe and Canada, the salmon louse, Lepeophtheirus salmonis (Krøyer), seriously affects the marine phase of salmon production. Although the problem is long-standing, the development of sustainable methods of pest management has been unable to keep pace with the intensification of production, leading to large-scale reliance on very few chemotherapeutants. This runs the risk of selecting for genetically determined resistance in target organisms. There are many examples of similar evolutionary adaptations in arthropod pests of arable crops, livestock and human health. Several hundred pest species are now documented as being resistant to one or more chemical classes of insecticides and acaricides. Many of these compounds are identical or closely related to ones currently employed against salmon lice. It is, therefore, opportune to consider what lessons have been learnt from contending with resistance in terrestrial organisms, the implications for sustainable use of chemotherapeutants in aquaculture, and the potential for developing effective resistance management strategies. An EU-funded project named SEARCH (QLK2-CT-2000-00809) has been initiated to explore in more detail the diagnosis, incidence, dynamics and management of resistance to chemotherapeutants in L salmonis.
Quinolones are currently the most commonly used group of antimicrobial agents in Norwegian aquaculture. The aims of this study were to examine and compare the pharmacokinetic properties of the quinolones oxolinic acid, flumequine, sarafloxacin, and enrofloxacin after intravascular and oral administration to Atlantic salmon (Salmo salar) by using identical experimental designs. The study was performed in seawater at 10.2 ؎ 0.2؇C with Atlantic salmon weighing 240 ؎ 50 g (mean ؎ standard deviation). The bioavailability varied considerably among the four quinolones. Following oral administration of medicated feed, the bioavailabilities of oxolinic acid, flumequine, sarafloxacin, and enrofloxacin were 30.1, 44.7, 2.2, and 55.5%, respectively. Taking the different dosages (25 mg/kg of body weight for oxolinic acid and flumequine and 10 mg/kg for sarafloxacin and enrofloxacin) into account, enrofloxacin showed the highest maximum concentration in plasma, followed by flumequine, oxolinic acid, and sarafloxacin. Following intravenous administration, the volumes of distribution at steady state of oxolinic acid, flumequine, sarafloxacin, and enrofloxacin were 5.4, 3.5, 2.3, and 6.1 liters/kg, respectively. Hence, all the quinolones showed good tissue penetration in Atlantic salmon. The elimination half-life of three of the quinolones, oxolinic acid, flumequine, and sarafloxacin, was less than or equal to 24 h, with oxolinic acid showing the shortest (18.2 h). On the other hand, the elimination half-life of enrofloxacin was estimated to be 34.2 h, almost twice that of oxolinic acid. This study showed that flumequine and enrofloxacin had better pharmacokinetic properties, compared with those of oxolinic acid, in Atlantic salmon held in seawater.In recent years, the quinolones oxolinic acid and flumequine have been the most frequently used antimicrobial agents in Norwegian aquaculture (17). Sarafloxacin, enrofloxacin, and other fluoroquinolones have showed enhanced in vitro activities compared with those of older quinolones, such as oxolinic acid and flumequine, against fish pathogenic bacteria (2, 21). Studies have also revealed better bactericidal activity (3, 16), as well as promising clinical efficacy in treatment of bacterial fish diseases (6,14,29). The chemical structures of oxolinic acid, flumequine, sarafloxacin, and enrofloxacin are shown in Fig. 1.The pharmacokinetic properties of quinolones have not been extensively studied in fish. However, there are several single reports indicating that their pharmacokinetic properties vary considerably from one compound to another (7,11,19,24). It is therefore important to clarify the pharmacokinetic properties of the different quinolones in fish, so as to be able to select the most beneficial compound for the treatment of bacterial fish diseases.Some data concerning the pharmacokinetic properties of oxolinic acid and flumequine in Atlantic salmon (Salmo salar) are available (11,12,24). As regards sarafloxacin and enrofloxacin in Atlantic salmon, one paper on the kinetics of s...
The plasma pharmacokinetic profile of the antibacterial agent florfenicol was studied in Atlantic salmon Salmo salar in seawater. In a single‐dose study, each fish was given 10 mg/kg body weight by intravenous (iv) injection or by oral gavage of feed coated with the drug. In a multidose study, pelleted feed coated with 2 g florfenicol/kg was hand‐fed daily for 10 d at a dosage of 10 mg florfenicol/kg body weight. The pellets contained small, X‐ray‐dense glass beads (hallotini). The feed intake was assessed by counting the number of ballotini on X‐ray pictures of sampled fish. In a depletion study, the concentration of the marker residue, florfenicol amine, was determined in muscle and liver after a field trial in which the fish were medicated with feed coated with florfenicol for 10 d at a dosage of 10 mg/kg body weight. In the single‐dose study, the iv data were best described by a two‐compartment open model; the elimination half time. t1/2β, was estimated at 14.7 h. The maximum plasma concentration was 9.l μg/mL, observed at 6 h. The bioavailability was 99%. The maximum plasma concentration observed in the multidose study and the maximum concentration predicted from the single‐dose study corresponded very well, which demonstrated the value of single‐dose studies. In the depletion study, the upper 95% confidence band for individual observations intercepted the limit of detection for the analytical method after 21 d in muscle and after 27 d in the liver.
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