Search

This study was performed to examine the appetite and the corresponding plasma and tissue distribution of florfenicol when administered to healthy groups of cod using medicated and non-medicated salmonid and marine feeds. Marine feed contains approximately 18% fat whereas salmonid feed contains approx. 30% fat. Two groups of fish were medicated with florfenicol at a dosage of 10 mg kg day for 10 consecutive days when the drug was administered either via marine or salmonid pellets. Two groups of fish also received either non-medicated marine or salmonid pellets. Twenty-four hours after giving the medicated marine feed, 14 out of 20 fish contained detectable concentrations of florfenicol with mean values (n = 14) of 4.67 ± 4.02 μg ml in plasma, 2.29 ± 2.11 μg g in muscle and 0.79 ± 0.69 μg g in the liver. In the fish given medicated salmonid feed, 18 of 20 fish contained detectable concentrations of florfenicol with mean values (n = 18) of 1.77 ± 1.84 μg ml in plasma, 0.75 ± 0.66 μg g in muscle and 0.30 ± 0.25 μg g in the liver. Decreased feed intake of the salmonid feed, both medicated and non-medicated, was noted when compared to medicated and non-medicated marine feed. No difference in feed consumption was registered between medicated and non-medicated marine feed, however a difference was noted between the medicated and non-medicated salmonid feed. [ABSTRACT FROM AUTHOR]

The pharmacokinetic profile of the antiparasitic agent emamectin benzoate was studied in plasma after intravenous (i.v.) injection and in plasma, muscle and skin following oral (p.o.) administration to cod, Gadus morhua, held in sea water at 9 °C and weighing 100–200 g. Following i.v. injection, the plasma drug concentration-time profile showed two distinct phases. The plasma distribution half-life ( t1/2α) was estimated as 2.5 h, the elimination half-life ( t1/2β) as 216 h, the total body clearance (ClT) as 0.0059 L kg−1 h−1 and mean residence time (MRT) as 385 h. The volume of distribution at steady state, Vd(ss), was calculated to be 1.839 L kg−1. Following p.o. administration the peak plasma concentration ( Cmax) was 15 ng mL−1, the time to peak plasma concentration ( Tmax) was 89 h and t1/2β was 180 h. The highest concentration in muscle (21 ng g−1) was measured after 7 days and t1/2β was calculated to be 247 h. For skin, a peak concentration of 28 ng g−1 at 3 days was observed and a t1/2β of 235 h was determined. The bioavailability following p.o. administration was calculated to be 38%. [ABSTRACT FROM AUTHOR]

Uptake, tissue distribution, metabolism and elimination of sulphadimethoxine (SDM) and ormetoprim (OMP) were examined in Atlantic cod ( Gadus morhua) following oral administration of Romet30 at a dose of 5 mg OMP and 25 mg SDM per kilogram fish. Absorption and elimination was rapid for OMP and slow for SDM characterized by peak plasma concentrations ( Cmax) of 1.44 and 20.93 μg ml−1 after 7 and 59 h, respectively, and plasma elimination halflives ( t1/2 β) of 7 h for OMP and 56 h for SDM. High concentrations of SDM were found in the bile indicating high biliary excretion of this drug whereas moderate concentrations of N-acetylated SDM were found in tissues and bile indicating N-acetylation to be a less important metabolic pathway for SDM in cod. The biliary concentration of OMP was low. [ABSTRACT FROM AUTHOR]

Uptake, tissue distribution, metabolism and elimination of sulphadimethoxine (SDM) and ormetoprim (OMP) were examined in Atlantic cod ( Gadus morhua) following oral administration of Romet30 at a dose of 5 mg OMP and 25 mg SDM per kilogram fish. Absorption and elimination was rapid for OMP and slow for SDM characterized by peak plasma concentrations ( Cmax) of 1.44 and 20.93 μg ml−1 after 7 and 59 h, respectively, and plasma elimination halflives ( t1/2 β) of 7 h for OMP and 56 h for SDM. High concentrations of SDM were found in the bile indicating high biliary excretion of this drug whereas moderate concentrations of N-acetylated SDM were found in tissues and bile indicating N-acetylation to be a less important metabolic pathway for SDM in cod. The biliary concentration of OMP was low. [ABSTRACT FROM AUTHOR]

Summary Administration of flumequine and oxolinic acid to turbot, Scophthalmus maximus L., by bath resulted in significant levels of both drugs in the muscle tissue. Bath treatment using 150 mg L-1 of flumequine and 200 mg L-1 of oxolinic acid for 72 h gave muscle concentrations of 10.2 and 6.2 μ g g-1 , respectively. Excretion of both antibacterials was rapid, reaching concentrations of 0.8 and 0.9 μ g g-1 , respectively, for flumequine and oxolinic acid 24 h after the end of treatment. At day 3 post-treatment the concentration of flumequine was below the limit of quantitation (0.1 μ g g-1 ) of the analytical method. Based on a minimum inhibitory concentration (MIC) of 0.0625 μ g ml-1 for susceptible strains, bath treatment maintain muscle levels in excess of 0.5 μ g ml-1 , corresponding to eight times the MIC-value for approximately 118 h for oxolinic acid and 104 h for flumequine. [ABSTRACT FROM AUTHOR]

The uptake, metabolism, tissue distribution and excretion of four sulphonamides and trimethoprim following bath treatment of Atlantic halibut, Hippoglossus hipoglossus L., were studied. Bath treatment using a concentration of 200 µg ml-1 for 72 h resulted in peak sulphadimidine concentrations in muscle and abdominal organ homogenates of 32.6 and 68.2 µg g-1, respectively. The corresponding values were 24.4 and 73.4 µg g-1 for sulphaguanidine, 6.1 and 45.1 µg g-1 for sulphamethoxazole, 2.1 and 15.1 µg g-1 for sulphadimethoxine, and 99 and 169 µg g-1 for trimethoprim. After a 72-h treatment, approximately 90% of the sulphadimethoxine and sulphamethoxazole present in tissues was found as the N4-acetylated metabolite, whereas for sulphadimidine and sulphaguanidine, the N4-acetylations were from 9 to 23%. Based on these preliminary absorption studies, sulphadimidine was chosen as the companion sulphonamide to trimethoprim. Using a combination of 500 µg sulphadimidine and 100 µg ml-1 trimethoprim in the bath for 72 h, peak muscle and liver concentrations of 262 and 312 µg g-1, respectively, for sulphadimidine and 32.8 and 83.6 µg g-1, respectively, for trimethoprim were achieved. Elimination half-lives (t½β) for sulphadimidine were calculated to be 35 and 48 h for muscle and liver, respectively. The corresponding values for trimethoprim were 98 and 116 h. Using the 95% confidence limit for single observations (95% prediction limit) and a maximum residue limit (MRL) value of 0.05 µg g-1 for trimethoprim and 0.1 µg g-1 for sulphadimidine, the elimination times (Et95) for muscle and liver were calculated to be 18 and 26 days, respectively, for sulphadimidine and 40 and 55 days, respectively, for trimethoprim. Minimum inhibitory concentrations (MIC) values against selected strains of Vibrio sp. were equal to or above 128 µg ml-1 for sulphadimidine, between 0.25 and 4.00 µg ml-1 for trimethoprim and between 0.4 and 8.8 µg ml-1 for various ratios of the sulphadimidine:trimethoprim combination. In the tested ratios, the combined antimicrobial action of trimethoprim and sulphadimidine were synergistic, as revealed by their fractional inhibitory concentration (FIC) indices. In general, the 1:5 trimethoprim sulphadimidine ratio showed the highest degree of synergism. Using a combination of 500 µg m-1 sulphadimidine and 100 µg ml-1 trimethoprim in the bath for 72 h, concentrations greater than a MIC value of 0.8 µg m-1 were maintained for 22 days in muscle and 29 days in liver. In a laboratory challenge experiment using Vibrio anguillarum strain HI 11347, a significantly lower mortality was observed in the drug-treated group (40%) compared to the untreated control group (93%). [ABSTRACT FROM AUTHOR]

The present authors have examined the survival of the fish pathogenic bacterium Vibrio salmonicida and the occurrence of antibiotic resistant bacteria in sediments from abandoned aquaculture sites. Survival of V. salmonicida was determined by fluorescent monoclonal antibody labelling combined with 4',6-diamidino-2-phenylindole (DAPI) staining. Using this method, the authors were able to detect V. salmonicida in sediment samples from six out of 12 abandoned fish farm locations. One out of the six positive stations was abandoned in 1982. Vibrio salmonicida was not detected at the three stations not affected by aquaculture (control locations) or in sediment samples taken 200-250 m away from aquaculture sites. When applying high-performance liquid chromatography, oxytetracycline or furazolidone residues were not detected in sediment samples from control or abandoned aquaculture sites. Nevertheless, the percentage of bacteria resistant to oxytetracycline was higher in aquaculture sediments, as compared to control sediments. The simultaneous occurrence of fish pathogens and high levels of resistant bacteria in sediments increases the risk of transfer of resistance to the pathogens. [ABSTRACT FROM AUTHOR]

The pharmacokinetic properties of the antibacterial agent oxolinic acid were studied after intravenous, intraperitoneal and oral administration to 1.5–3.0 kg Atlantic halibut, Hippoglossus hippoglossus L., held in sea water at 9 °C. Following intravenous injection, the plasma drug concentration-time profile showed two distinct phases. The terminal elimination half-life was estimated to be 52 h, whereas total body clearance (ClT) was determined to be 0.044 L kg–1 h–1. The volume of distribution at steady state, Vd(ss), was calculated to be 3.0 L kg–1, indicating good tissue penetration of oxolinic acid in Atlantic halibut. The peak plasma concentration (Cmax) and the time to peak plasma concentration (Tmax) were estimated to be 1.2 and 2.7 μg mL–1, and 21.5 and 80 h, respectively, following oral administration of medicated feed or intraperitoneal injection. The corresponding bioavailabilities were calculated to be 15% and 92%, respectively. Oral administration of vetoquinol, the carbitol ester of oxolinic acid, increased the bioavailability of oxolinic acid to 64% and the total bioavailability (oxolinic acid + vetoquinol) to 82%, whereas Cmax and Tmax values of 6.7 μg mL–1 and 14.5 h, respectively, for oxolinic acid, and 1.0 μg mL–1 and 6.3 h, respectively, for vetoquinol were obtained. Based on a minimum inhibitory concentration (MIC) of 0.0625 μg mL–1 for susceptible strains, a single intraperitoneal injection of 25 mg kg–1 of oxolinic acid maintains plasma levels in excess of 0.25 μg mL–1, corresponding to four times the MIC value, for ≈12 days. The corresponding values for a single oral dose of 25 mg kg–1 of oxolinic acid and vetoquinol were 5 and 10 days,... [ABSTRACT FROM AUTHOR]

The pharmacokinetic properties of the antibacterial agent oxolinic acid and vetoquinol, the carbitol ester of oxolinic acid, were studied after intravenous (i.v.) and oral (p.o.) administration to 100-150 g cod, Gadus morhua L., held in sea water at 8 degrees C. Following i.v. injection, the plasma drug concentration-time profile showed two distinct phases. The distribution half-life (t1/2alpha) was estimated at 1.3 h, the elimination half-life (t1/2beta) as 84 h and the total body clearance (Cl(T)) as 0.047 L kg(-1) h(-1). The volume of distribution at steady state, Vd(ss) was calculated to be 5.5 L kg(-1), indicating good tissue penetration of oxolinic acid in cod. Following p.o. administration of oxolinic acid or vetoquinol, the peak plasma concentrations (C(max)) of oxolinic acid and the time to peak plasma concentrations (T(max) were estimated to be 1.2 and 2.5 microg mL(-1) and 24 and 12 h, respectively. The bioavailabilities of oxolinic acid following p.o. administration of oxolinic acid and vetoquinol were calculated to be 55 and 72%, respectively. The in vitro minimum inhibitory concentration (MIC) values of oxolinic acid against three strains of Vibrio anguillarum isolated from diseased cod were 0.016 microg mL(-1) (HI-610), 0.250 microg mL(-1) (HI-618) and 0.250 microg mL(-1) (HI-A21). Based on a MIC value of 0.016 microg mmL(-1) a single p.o. administration of 25 mg kg(-1) of oxolinic acid maintains plasma levels in excess of 0.064 microg mL(-1), corresponding to four times the MIC-value, for approximately 12 days. The analogous value for a single p.o. dose of 25 mg kg(-1) of oxolinic acid administered as vetoquinol was 13 days.

After substantial investments in research, the Atlantic halibut Hippoglossus hippoglossus is now being cultivated commercially in Norway, Iceland, Scotland and Canada. As with other domesticated species, disease problems have been experienced. This review summarizes the current state of knowledge of diseases of the Atlantic halibut, and their diagnosis, prophylaxis and treatment. In economic terms, the most important losses have been suffered at the larval and juvenile stages. The most important infections are caused by nodaviruses, causative agents of Viral Encephalopathy and Retinopathy (VER), which are the major reason why Norway's production of halibut fry has been level since 1995. An aquatic birnavirus, Infectious Pancreatic Necrosis Virus, is also an important agent of mortality. Vibrio anguillarum, Flexibacter ovolyticus and atypical Aeromonas salmonicida are the major bacterial pathogens. The protozoan parasites recorded include Ichthyobodo sp., the microsporidium Enterocytozoon sp., Trichodina hippoglossi, and the metazoan pathogens include myxozoans, helminths, Entobdella hippoglossi, Lepeophtheirus hippoglossi and other parasitic copepods. Experimental vaccines have been tested against V anguillarum and atypical A. salmonicida, with good results. A recombinant vaccine against nodaviruses is under development. A few trials have been carried out on non-specific immunostimulants, but no such treatment is currently available. A number of efficacy and pharmacokinetic trials with various antibacterial agents have also been published.

This study was performed to determine the efficacy of orally administered oxolinic acid and Vetoquinol, an oxolinic acid ester, in the treatment of experimental induced furunculosis in Atlantic salmon Salmo salar held in seawater. Two strains of the causative bacterium Aeromonas salmonicida subsp. salmonicida, 1 sensitive (VI-88/09/03175) and 1 resistant (3475/90) to oxolinic acid, were used. In 2 trials, cohabitational challenges were performed by introducing 8 fish challenged in advance by an intraperitoneal injection of 2.2 x 10(4) colony forming units of strain 3475/90 (Trial 1) or strain VI-88/09/03175 (Trial 2) to 10 aquaria each containing 40 healthy fish. The treatment groups in both trials consisted of 4 groups receiving either oxolinic acid (2 groups) or Vetoquinol (2 groups) and 1 control group. An unchallenged, unmedicated group was used to determine the natural mortality in the population. The recommended therapeutic dose of 25 mg oxolinic acid kg-1 fish at Days 1, 2, 4, 6, 8 and 10 following initiation of treatment was used. Oral medication initiated at Day 10 (Trial 1) or Day 11 (Trial 2) following challenge significantly (p < 0.05) lowered the specific mortality in all drug-treated groups compared to the untreated control groups. Mortality in Vetoquinol-treated groups was significantly (p < 0.05) lower than in oxolinic acid-treated groups in Trial 1 whereas no significant (p < 0.05) difference in survival rate was found between the medicated groups in Trial 2.

A rapid clean-up and high-performance liquid chromatographic method for the simultaneous determination of ormethoprim and sulphadimethoxine in plasma and muscle of Atlantic salmon (Salmo salar) has been developed. Sample preparation is based on protein precipitation using trichloroacetic acid or methanol for plasma and muscle, respectively. The drugs are separated using a reversed-phase C18 analytical column and phosphate buffer-acetonitrile (80:20, v/v) containing 1-heptanesodiumsulphonate and triethylamine, as mobile phase. Detection was performed at 270 nm. The average recovery of ormethoprim was 97.2% in muscle and 95.7% in plasma, whereas the average recovery of sulphadimethoxine was 86.5% in muscle and 90.2% in plasma. The limit of detection at a signal-to-noise ratio of 3 was 50 ng/g and 30 ng/ml for ormethoprim in muscle and plasma respectively and 30 ng/g and 15 ng/ml in muscle and plasma respectively for sulphadimethoxine.

Following 10 days medication with oxytetracycline, marine sediment was sampled beneath three selected cages (cages 1, 2 and 3) at a fish farm over a period of 18 mnd., in order to detect any change in the sediment oxytetracycline concentration, bacterial number and bacterial resistance towards the drug. The bulk of oxytetracycline disappeared during the first weeks, but it persisted in the sediment at lower concentrations for quite some time after the medication. Half-life (t(1/2)) of oxytetracycline in the sediment was measured as: 125, 144 and 87 days under cages 1, 2 and 3, respectively. At the end of the medication, all three sediments had greater than 100% oxytetracycline-resistant bacteria. This value dropped to 20% after 72 days and stabilised at levels of between 10 and 50%. The change in bacterial numbers, described as total and plate counts, was due to seasonal variations rather than to the medication.

Furazolidone is used in the treatment of bacterial diseases in farmed fish. During application a large proportion of the administered drug reaches the environment directly or via feces. The persistence and metabolism of furazolidone in sediment from a Norwegian salmon farm is described. Furazolidone, in contrast to oxytetracycline and oxolinic acid, is actively metabolized by microorganisms in the sediment. The main metabolite is 3-(4-cyano-2-oxobutylidene-amino)-2-oxazolidone. This is a well known metabolite of the degradation of furazolidone in mammals, fish and Escherichia coli. 3-(4-Cyano-2-oxobutylideneamino)-2- oxazolidone had no detectable antibacterial activity. The half-life of furazolidone in the sediment at 4 degrees C was calculated to be 18 h.

The metabolism of o-methoxycinnamaldehyde (1.3 mmol/kg, intragastrically) was studied in rats. Identification of the urinary metabolites by g.l.c.-mass spectrometry and quantification by h.p.l.c. showed that the major metabolic pathway (approx. two-thirds of the dose) was oxidation to the corresponding cinnamic and phenylpropionic acids (C6-C3 acids) which were largely excreted as glycine conjugates. Intermediate amounts (approx. 10% of the dose) of the O-demethylated C6-C3 acids were excreted. Relatively large amounts of the beta-hydroxylated phenylpropionic acid derivative were found, however only traces of the further products of beta-oxidation (2-methoxylated derivatives of benzoic and hippuric acid) were excreted. No evidence was obtained for conjugation of o-methoxycinnamaldehyde with glutathione. Urinary excretion of metabolites was rapid (91% in 24 h and 98% in 48 h).