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...

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The in vitro antimicrobial activities of oxolinic acid, flumequine, sarafloxacin, enrofloxacin, and oxytetracycline against strains of bacteria pathogenic to fish (Aerononas salmonicida subsp. salmonicida, atypical A. salmonicida, Vibrio sabnonicida, Vibrio anguillarum, and Yersinia ruckeri) were determined at two different incubation temperatures, 4 and 15°C, by a drug microdilution method. The main objective of the study was to examine the effect of incubation temperature on the in vitro activities of 4-quinolones and oxytetracycline against these bacteria. When tested against A. salmonicida subsp. salmonicida, all of the quinolones examined had MICs two-to threefold higher at 4°C than at 15°C. Similarly, 1.5-to 2-fold higher MICs were recorded for all of the quinolones except sarafloxacin at 4°C than at 15°C when the drugs were tested against V. salmonicida. In contrast to those of the quinolones, the MICs of oxytetracycline were two-to eightfold lower at 4°C than at 15°C against all of the bacterial species tested. Of the antimicrobial agents tested against the bacterial species included in the study, enrofloxacin was the most active and oxytetracycline was the least active. Sarafloxacin was slightly more active than flumequine and oxolinic acid, especially against oxolinic acid-resistant A. salmonicida subsp. salmonicida strains.In recent years, the 4-quinolone antimicrobial compounds oxolinic acid and flumequine, in addition to oxytetracycline, and sulfadiazine-trimethoprim, have been the most frequently used antimicrobial agents in Norwegian aquaculture (18,23).Substantial development of oxolinic acid and tetracycline resistance in bacteria pathogenic to fish (2, 19, 29, 31) has led to a need for new antimicrobial drugs for control of bacterial fish diseases in aquaculture. Aminopenicillins, several sulfonamide-trimethoprim combinations, chloramphenicol analogs such as thiamphenicol and florfenicol, and potent fluoroquinolones have all been proposed and tested as potential new drug candidates (2,3,12,16,21,24,25,30).Several of the new fluoroquinolones generated during the last decade (32) show increased inhibitory (6, 15) and bactericidal (4) activities in vitro against many bacterial pathogens, compared with the old 4-quinolones, such as nalidixic acid and oxolinic acid. Studies have also revealed that the newer compounds show increased potency (2, 25), as well as more effective bactericidal activity (3, 21), against bacteria pathogenic to fish.Along the Norwegian coastline, there are significant seasonal and geographic seawater temperature variations, from just above zero in the winter to well above 18°C in the summer at the same site. The most common bacterial fish diseases in Norway, furunculosis, vibriosis, cold water vibriosis, bacterial kidney disease, yersiniosis, and infections caused by different strains of atypical Aeromonas salmonicida, may all occur at a wide range of temperatures.The general influence of temperature on the pharmacoki-

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