A single-dose pharmacokinetic study of oxolinic acid and vetoquinol,an oxolinic acid ester,in cod,Gadus morhua L., held in sea water at 8 degrees C and in vitro antibacterial activity of oxolinic acid against Vibrio anguillarum strains isolated from diseased cod

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.     

Pharmacokinetics of oxolinic acid in black tiger shrimp, Penaeus monodon Fabricius, and the effect of cooking on residues

This study examined the pharmacokinetics and bioavailability of oxolinic acid (OA) in black tiger shrimp Penaeus monodon Fabricius, in brackish water (salinity 10 g L^?1) at 28–29°C, after intra‐sinus (10 mg kg^?1) and oral (50 mg kg^?1) administration and also investigated the net changes of OA residues in the shrimp after cooking (boiling, baking and frying). The haemolymph concentrations of OA after intra‐sinus dosing were best described by a two‐compartment open model. The distribution and elimination half‐lives were 0.84 and 17.7 h respectively. The apparent volume of distribution at a steady state and the total body clearance were estimated to be 2061 mL kg^?1 and 90.1 mL kg^?1 h^?1 respectively. The bioavailability of OA after an oral administration was 7.9%. The peak haemolymph concentration, the time to peak haemolymph concentration and the elimination half‐life after oral administration were 4.20 μg mL^?1, 4 h and 19.8 h respectively. Oxolinic acid muscle and shell levels increased to a maximum (muscle 1.76 μg g^?1 and shell 8.17 μg g^?1) at 4 h post administration and then decreased with the elimination half‐life value of 20.2 and 21.9 h respectively. Residual OA in muscle and shell was reduced by 20–30% by each cooking procedure examined.     

Multiple dose pharmacokinetic study of oxolinic acid in cod, Gadus morhua L.

The plasma, muscle and liver distribution and elimination of the antibacterial agent oxolinic acid were studied after multiple oral (p.o.) administration of 10 or 20 mg kg⁻¹ day⁻¹ to cod (Gadus morhua) for 6 days. The fish, held in seawater at 6 and 12°C and weighing 150–250 g were sampled 24 h following last medication. The concentrations in plasma and tissues were clearly dosage and temperature dependent. The distribution from plasma to muscle (muscle/plasma ratio) was higher than that from a single dose study and independent of temperature and dosage. The distribution from plasma to liver (liver/plasma ratio) was lower than the muscle/plasma ratio and according to this study dependent of the administered dosage but independent of temperature. The elimination of oxolinic acid from plasma, muscle and liver was considerably faster following multiple administration compared to a single administration.     

Pharmacokinetic/pharmacodynamic properties and P‐glycoprotein expression in pacific white shrimp,Litopenaeus vannamei after oral administration at three dosages of oxolinic acid

The experiments explored the pharmacokinetics (PK) properties of oxolinic acid (OXA) after oral administration at three dosages (10, 30 and 80 mg/kg) via medicated feed in the shrimp. The results showed that the C_max values of 4.31, 14.93 and 16.62 mg/L and AUC_0–∞ values of 92.61, 252.30 and 364.27 mg hr^?1 L^?1 were observed at three OXA dosage groups in the haemolymph respectively. In the hepatopancreas, C_max values of 7.90, 27.23 and 60.51 mg/kg and AUC_0–∞ values of 42.01, 133.06 and 219.06 mg hr^?1 L^?1 were observed at 0.5 hr post administration respectively. In the muscle, C_max values of 1.62, 5.80 and 7.36 mg/kg and the AUC_0–∞ values of 25.64, 98.10 and 134.24 mg hr^?1 L^?1 were observed at 2 hr post administration respectively. In the gills, C_max values of 2.87, 8.08 and 12.12 mg/kg and the AUC_0–∞ values of 51.38, 118.65 and 206.48 mg hr^?1 L^?1 were observed at 4 hr post administration respectively. In addition, the in vitro MIC values of OXA at three dosages against 132 strains of Vibrio were examined and showed that the minimum inhibitory concentration (MIC) values for OXA primarily ranged from 0.15–1.25 µg/ml, including eight strains of Vibrio showing MIC values ≥5 µg/ml. The MIC₅₀ and MIC₉₀ values of 132 strains were 0.62 and 1.25 μg/ml respectively. The AUC_0–24/MIC₉₀ ratios of Vibrio were 140.4 in 30 mg/kg group. Furthermore, the P‐glycoprotein (P‐gp) expression was determined in shrimp tissues after administration to three dosage groups (10, 30 and 80 mg/kg). The results showed that P‐gp expression was up‐regulated in the hepatopancreas (5.36‐, 13.68‐ and 31.06‐fold respectively) compared with the control group.     

The kinetic profile of oxolinic acid in sharpsnout sea bream, Diplodus puntazzo (Cetti 1777)

The pharmacokinetics of oxolinic acid (OA) were investigated after a single intra‐vascular injection (20 mg kg^?1 fish) in sharpsnout sea bream (90 g), a promising new euryhaline species for Mediterranean fish farming. The distribution half‐life (t_1/2α) and the elimination half‐life (t_1/2β) of OA were calculated to be 0.4 and 10 h respectively. The apparent volume of distribution at steady‐state (V_d(ss)) and total clearance rate (CL_T) of the drug were found to be 2.1 L kg and 0.2 L kg^?1 h^?1 respectively. The bioavailability (F%) of OA following oral administration (40 mg kg^?1 fish) was estimated to be 15%. The results indicate a rapid distribution and elimination of the drug, moderate tissue penetration, but low absorption in sharpsnout sea bream. The kinetic profile of OA found in this species is comparable with that observed in another well‐known sparid, gilthead sea bream.     

Pharmacokinetics and tissue residues of marbofloxacin in crucian carp (Carassius auratus) after oral administration

Pharmacokinetics and residue elimination of marbofloxacin (MBF) were studied in crucian carp (Carassius auratus, 250±30 g) kept at two water temperatures of 15 and 25 °C. Marbofloxacin concentrations in plasma and tissues were analysed by means of high‐performance liquid chromatography using an ultraviolet detector. The limits of detection were 0.02 μg mL^?1, 0.02 μg g^?1, 0.025 μg g^?1, 0.02 μg g^?1 and 0.025 μg g^?1 in plasma and muscle, skin, liver and kidney respectively. Fish were administered orally at a single dosage of 10 mg kg^?1 body weight in the PK group. The data were fitted to two‐compartment open models at both temperatures. At 15 °C, the absorption half‐life () and distribution half‐life (t_1/2α) of the drug were 0.36 and 4.48 h respectively. The corresponding values at 25 °C were 0.23 and 0.87 h respectively. The elimination half‐life (t_1/2β) was 50.75 h at 15 °C and 25.05 h at 25 °C. The maximum MBF concentration (C_max) differed little between 15 (6.43 μg mL^?1) and 25 °C (8.36 μg mL^?1). The time to peak concentration was 1.74 h at 15 °C and 0.78 h at 25 °C. The apparent volume of distribution (V_d/F) of MBF was estimated to be 1.36 and 0.87 L kg^?1 at 15 and 25 °C respectively. The area under the concentration–time curve (AUC) was 301.80 μg mL^?1 h at 15 °C and 182.80 μg mL^?1 h at 25 °C. The total clearance of MBF was computed as 0.03 and 0.05 L h^?1 kg^?1 at 15 and 25 °C respectively. After repeated oral administration at a dosage of 10 mg kg^?1 body weight per day for 3 days, the results showed that the elimination half‐lives () of MBF from all tissues at 15 °C were longer than that at 25 °C. Therefore, water temperature is an important factor to be considered when deciding a reasonable withdrawal time.     

A single‐dose pharmacokinetic study of emamectin benzoate in cod,Gadus morhua L., held in sea water at 9 °C

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 (t_1/2α) was estimated as 2.5 h, the elimination half‐life (t_1/2β) as 216 h, the total body clearance (Cl_T) as 0.0059 L kg^?1 h^?1 and mean residence time (MRT) as 385 h. The volume of distribution at steady state, V_d(ss), was calculated to be 1.839 L kg^?1. Following p.o. administration the peak plasma concentration (C_max) was 15 ng mL^?1, the time to peak plasma concentration (T_max) was 89 h and t_1/2β was 180 h. The highest concentration in muscle (21 ng g^?1) was measured after 7 days and t_1/2β was calculated to be 247 h. For skin, a peak concentration of 28 ng g^?1 at 3 days was observed and a t_1/2β of 235 h was determined. The bioavailability following p.o. administration was calculated to be 38%.     

Temperature-dependent pharmacokinetics and tissue distribution of oxolinic acid in sea bass, Dicentrarchus labrax L., after a single intravascular injection

The pharmacokinetics and tissue distribution of oxolinic acid following an intravascular administration (15 mg kg^?1 fish) were determined in sea bass, Dicentrarchus labrax L. (110 g), at 13 °C and 22 °C water temperature. The kinetic profile of the drug was found to be temperature dependent, with increased temperature having a greater effect on distribution after equilibrium and the elimination phase than on the distribution process. The distibution half‐life of oxolinic acid was 1.15 and 2.76 h at 22 °C and 13 °C respectively, whereas the elimination half‐life of the drug was 55 h at 22 °C and 315 h at 13 °C. The values of the apparent volume of distribution (1.44 L kg^?1 at 22 °C and 3.31 L kg^?1 at 13 °C) and the volume of distribution at steady state (5.2 and 14.7 L kg^?1 at the high and low temperature respectively) were considerably different between the two tested temperatures. The total body clearance of the antibiotic was found to be low (1.47 L kg^?1 day^?1 at 22 °C and 0.80 L kg^?1 day^?1 at 13 °C). Lower rates of elimination were found for the liver compared with muscle, the difference increasing with increasing temperature, while elimination rates from the serum were higher than those of other tissues, especially at the high temperature.     

Pharmacokinetics of florfenicol and behaviour of its metabolite florfenicol amine in orange‐spotted grouper (Epinephelus coioides) after oral administration

Pharmacokinetics and elimination of florfenicol and florfenicol amine in grouper held in sea water at 23.3 ± 0.8 °C were studied using HPLC method after they were given a single peroral dose of florfenicol at 24 mg kg^?1 body weight. Florfenicol was rapidly absorbed from intestine and distributed extensively to all the tissues examined. The maximum concentrations (C_max, μg g^?1 or μg mL^?1) in plasma and tissues were observed at 2–6 h (the time to reach maximum concentration, T_max) except for bile (T_max = 24 h) and were in the order of intestine (52.02 ± 25.07) > bile (49.41 ± 28.16) > gill (45.12 ± 11.10) > plasma (28.28 ± 5.43) > liver (21.97 ± 12.08) > muscle (21.63 ± 6.12) > kidney (20.88 ± 11.28) > skin (19.10 ± 5.88). The drug distribution level was higher in plasma than in extravascular tissues except for bile, based on the ratios of the area under concentration–time curve between tissue and plasma (AUC_{tissue/plasma}). The elimination of florfenicol was rapid in fish, and the corresponding half‐lives (T_1/2β) in the order of magnitude were bile (13.92 h) > muscle or liver (12.31 h) > skin (11.77 h) > plasma (11.57) > gill (11.04 h) > intestine (10.55 h) > kidney (10.05 h). The delayed T_max, lower C_max and longer T_1/2β for florfenicol amine compared with florfenicol were measured in grouper.     

Pharmacokinetics of oxolinic acid and oxytetracycline in kuruma shrimp, Penaeus japonicus

The pharmacokinetics of oxolinic acid and oxytetracycline were examined in kuruma shrimp (Penaeus japonicus) after intra-sinus (10 and 25 mg/kg, respectively) and oral (50 mg/kg) administration. The shrimp were kept in tanks with recirculated artificial seawater at a salinity of 22–23 ppt. The water temperature was maintained at 25±0.6 °C. The hemolymph concentrations of both drugs after intra-sinus dosing were best described by a two-compartment open model. The distribution and elimination half-lives (t_1/2 and t_1/2β) were found to be 0.59 and 33.2 h for oxolinic acid and 0.45 and 24.7 h for oxytetracycline, respectively. The apparent volume of distribution at a steady state (V_ss) and total body clearance (CL_b) were estimated to be 1309 ml/kg and 28.8 ml/kg/h for oxolinic acid and 748 ml/kg and 22.7 ml/kg/h, respectively. The hemolymph concentration–time curves after oral administration did not fit by the nonlinear least squares method using one- and two-compartment model with first-order absorption in either of the drugs. The peak hemolymph concentration (C_max), the time to peak hemolymph concentration (t_max) and the elimination half-life were found to be 17.8 μg/ml, 7 h and 34.3 h for oxolinic acid and 24.3 μg/ml, 10 h and 33.6 h for oxytetracycline, respectively. The bioavailability (F) after oral administration was 32.9% for oxolinic acid and 43.2% for oxytetracycline. The hemolymph protein binding in vivo was determined to be 36.7±8.5% for oxolinic acid and 22.9±4.8% for oxytetracycline.     

Pharmacokinetic model of florfenicol in turbot (Scophthalmus maximus): establishment of optimal dosage and administration in medicated feed

The pharmacokinetics of florfenicol (FF) in turbot (Scophthalmus maximus) was studied after single intravenous (10 mg kg⁻¹) and oral (100 mg kg⁻¹) administration. The plasma concentration–time data of florfenicol were described by an open one‐compartment model. The elimination half‐life (t_1/2) was estimated to be 21.0 h, and the total body clearance, Cl, was determined as 0.028 L kg h⁻¹. The apparent volume distribution (V_d) was calculated to be 0.86 L kg⁻¹ and the mean residence time (MRT_iv) was 30.2 h. Following oral administration, the maximum plasma concentration (C_max) of 55.4 μg mL⁻¹ was reached at 12 h (T_max). The absorption constant (k_a) was 0.158 h⁻¹. The bioavailability was estimated to be 57.1%. The low bioavailability observed at higher doses was explained by the saturation of the mechanisms of absorption. The drug absorption process was limited by its inherent low solubility, which limited the amount of available FF absorbed in the gastrointestinal tract. Based on the pharmacokinetic data, an optimal dosing schedule for FF administration is hereby provided. Based on the minimum inhibitory concentration found for susceptible strains of Aeromonas salmonicida, oral FF administration of first, an initial dose of 30 mg FF kg⁻¹, followed by 6 maintenance doses at 18 mg kg⁻¹/daily could be effective against furunculosis in turbot.     

Bioencapsulation and pharmacokinetic study of oxolinic acid in rotifers (Brachionus plicatilis), Artemia franciscana nauplii and metanauplii

The uptake of oxolinic acid by the rotifer Brachionus plicatilis, Artemia franciscana nauplii and metanauplii was studied as a function of its concentration in the enrichment medium and the duration of the enrichment period. An emulsion containing 5, 10, 20 or 30% (w/w) oxolinic acid was administered and the enrichment period lasted 4, 8, 12 or 36 h. Highest incorporation of oxolinic acid was achieved using a 20% emulsion and a 12 h enrichment for rotifers (205.05 ± 17.1 μg g^?1 dry weight), a 24 h enrichment for nauplii (2528.8 ± 254.6 μg g^?1 dry weight), and an 8 h enrichment for metanauplii (1236.58 ± 22.9 μg g^?1 dry weight). Higher concentrations of oxolinic acid in the enrichment emulsion or longer enrichment times resulted in decreased survival. Two hours post enrichment the contents of the drug appeared significantly decreased. The concentration data of oxolinic acid were best fit to a two phase exponential elimination model, the first phase elimination half‐life (t_1/2α) being 1.86, 1.08 and 1.74 and the terminal phase elimination half‐life (t_1/2β) 26.83, 29.67 and 17.48 in rotifers, nauplii and metanauplii correspondingly. Enrichment with an emulsion containing 20% oxolinic acid is recommended employing a duration of 12, 24, or 8 h enrichment for rotifers, nauplii and metanauplii respectively, while enriched carriers should be used shortly after enrichment.     

Pharmacokinetic disposition of enrofloxacin in brown trout (Salmo trutta fario) after oral and intravenous administrations

In this study, the pharmacokinetic profile of enrofloxacin (EF) and its major metabolite, ciprofloxacin (CF), were investigated in brown trout (Salmo trutta fario) (n = 150) after intravenous (i.v.) and oral (p.o.) administrations of a single dose of 10 mg kg^− 1 body weight (b.w.) at 10 °C. The plasma concentrations of the drugs were determined by high-performance liquid chromatography (HPLC-UV) from 0.08 to 120 h. Pharmacokinetic parameters were described by the two-compartment open model for intravenous and oral administrations, respectively. After intravenous administration, the elimination half-life (t_1/2β), apparent volume of distribution at steady-state (V_ss) and total body clearance (Cl_tot) of enrofloxacin were 19.14 ± 1.51 h, 3.40 ± 0.18 L kg^− 1 and 0.14 ± 0.01 L kg h^− 1, respectively. After oral administration, the maximum plasma concentration (C_max), time of maximum concentration (t_max) and bioavailability (F%) were 2.30 ± 0.08 µg mL^− 1, 8 h and 78 ± 4%, respectively. Ciprofloxacin was not detected in the present study. The elimination half-life for enrofloxacin following oral administration was longer than values calculated for other animals. After oral administration, the mean plasma concentration was well above the minimum inhibitory concentrations (MICs)—that is, > 0.5 µg mL^− 1 at 36 h—for most gram-negative fish pathogens. It is possible and practical to obtain therapeutic blood concentrations of enrofloxacin in brown trout (S. trutta fario) using oral administration of 10 mg kg^− 1 body weight; therefore, it may be effective in the therapy for brown trout diseases.     

Pharmacokinetic and efficacy studies on bath-administering potentiated sulphonamides in Atlantic halibut, Hippoglossus hippoglossus L.

The uptake, metabolism, tissue distribution and excretion of four sulphonamides and trimethoprim following bath treatment of Atlantic halibut, Hippoglossus hippoglossus 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 ml^–1 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 (t_1/2β) 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 (E_t95) 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 ml^–1 sulphadimidine and 100 μg ml^–1 trimethoprim in the bath for 72 h, concentrations greater than a MIC value of 0·8 μg ml^–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%).     

Free amino acid distribution in plasma and liver of juvenile cobia (Rachycentron canadum) fed increased levels of lizardfish silage

Juvenile cobia (Rachycentron canadum) (100 g) were fed four moist diets (447–476 g kg^?1 dry wt) where 0, 130, 260 or 390 g kg^?1 of concentrated lizardfish (Saurida undosquamis) silage replaced fresh lizardfish, respectively. Blood and livers were sampled at 0, 6, 12, 24 and 48 h postfeeding at the end of the 3‐week experiment. At 6 h postfeeding in all groups, maximum concentrations of most plasma essential amino acids were observed, while significantly lower levels of most non‐essential amino acid levels were recorded compared to the other sampled times. At 6 and 12 h after feeding, the concentration of most plasma free amino acid (FAA) increased with an increase in dietary fish silage levels. Most FAA in livers of all groups peaked at 12 and 24 h postfeeding. However, at 48 h postfeeding, concentrations of most plasma FAA were significantly higher in fish fed 0% silage‐based diet than in fish fed the other diets (4999 versus 3390–4339 nmol AA mL^?1 plasma). Growth rates and feed utilization were significantly lower in cobia fed 26% or 39% silage‐based diets than in fish fed 0% or 13% silage‐based diets. Different levels of silage protein thus seemed to have effects on growth and feed utilization efficiency of juvenile cobia. Results from this study support the premise that fish silage can be included until 130 g kg^?1 in cobia diets.     

Pharmacokinetics and bioavailability of flumequine and oxolinic acid after various routes of administration to Atlantic salmon in seawater

The present preclinical study was performed to investigate the pharmacokinetics of flumequine in Atlantic salmon (Salmo salar L.) in seawater after administration of different doses and dosage formulations. Flumequine was administered intravenously (dose 4.9 mg/kg fish) and orally from the drug delivery system Aqualets as Apoquin 5 g/kg (dose 25 mg/kg) and 10 g/kg (dose 50 mg/kg), respectively. Experiments were carried out with oxolinic acid administered in the same way for the purpose of comparing the two compounds. The seawater temperature was 5±0.2°C in all experiments.

The pharmacokinetic calculations showed that the distribution half-life for flumequine was and for oxolinic acid . The drugs were absorbed rapidly, and flumequine reached a plasma concentration of C_max = 2.26 μg/ml after a single oral dose of 25 mg/kg, whereas oxolinic acid reached C_max = 0.99 μg/ml. The apparent bioavailability of flumequine was found to be 40–45%, whereas the apparent bioavailability of oxolinic acid varied from 25% at a dose of 50 mg to 40% at a dose of 25 mg/kg body weight of fish. The distribution profile of flumequine in the various compartment of fish appeared to be different from that of oxolinic acid. After a single oral dose (25 mg/kg) the areas under the concentration-time curves showed that flumequine was 2.3 times more concentrated in plasma and 2.6 times more concentrated in liver compared to oxolinic acid. In muscle the difference was less pronounced, flumequine being 1.4 times more concentrated than oxolinic acid.     

恶喹酸与诺氟沙星对异育银鲫体内嗜水气单胞菌的抑菌效果比较

在水温(25±2)℃下,给体质量150~200g的异育银鲫分别口灌3种剂量(20、30、40mg/kg)的诺氟沙星和恶喹酸,结合这两种药物对嗜水气单胞菌AH10的体外药效学研究和对异育银鲫单次口灌不同剂量的诺氟沙星、恶喹酸的体内药代动力学,研究诺氟沙星、恶喹酸对异育银鲫体内嗜水气单胞菌AH10的抑菌效果。试验结果表明,恶喹酸和诺氟沙星对嗜水气单胞菌AH10的最小抑菌质量浓度分别为1μg/mL和0.5μg/mL。口灌上述3种剂量恶喹酸、诺氟沙星后,异育银鲫血浆中恶喹酸的最大药物质量浓度分别为4.1μg/mL、6.0μg/mL和8.89μg/mL;诺氟沙星的最大药物质量浓度分别为11.5μg/mL、15.1μg/mL和18.9μg/mL;恶喹酸的最大药物质量浓度/最小抑菌质量浓度分别为4.1、6.0和8.89;诺氟沙星的最大药物质量浓度/最小抑菌质量浓度分别为23、30.2和37.8;恶喹酸0~24h内药—时曲线下面积/最小抑菌质量浓度分别为21.6214、33.1449、39.1846;诺氟沙星0~24h内药—时曲线下面积/最小抑菌质量浓度分别为274.75、451.55、578.35。综合0~24h内药—时曲线下面积/最小抑菌质量浓度、最大药物质量浓度/最小抑菌质量浓度这两个指标可知,诺氟沙星对异育银鲫体内的嗜水气单胞菌AH10抑制效果强于恶喹酸。     

Pharmacokinetics of oxolinic acid in gilthead sea bream, Sparus aurata L.

This is the first study on the pharmacokinetic parameters of oxolinic acid (OA) in gilthead sea bream, Sparus aurata L. The kinetic profile of OA was studied after a single intravascular injection (20 mg kg⁻¹) in 100 g fish at 20 °C. The distribution half-life ( t _1/2α) and the elimination half-life ( t _1/2β) of the drug were found to be short (0.51 and 12.60 h, respectively). The drug penetration from the plasma to the tissues was adequate as the apparent volume of distribution of the drug at steady-state ( V _d(ss)) was found to be 2.11 L kg⁻¹. The mean residence time ( MRT ) of OA was short (14.25 h) and the total clearance rate ( Cl _T) of the drug was low (0.15 L kg⁻¹ h⁻¹). The bioavailability ( F %) of OA following oral administration (30 mg kg⁻¹) was also low (14%). Maximum values were observed for muscle at 0.5 h after injection, with levels declining as with subsequent sampling. At the first two time points (0.5 and 1 h) plasma levels of OA were higher than muscle, however, the reverse was evident for subsequent samples. Following oral administration, highest muscle levels were found at 16 h and, with the exception of the 24-h sampling, muscle OA concentrations were higher than plasma at all time points. The fast elimination of OA suggests short withdrawal times with reference to human consumption of treated fish.     

Low levels of Aflatoxin B1 could cause mortalities in juvenile hybrid sturgeon,Acipenser ruthenus ♂×A. baeri♀

Toxicity of aflatoxin B₁ (AFB₁) was investigated in juvenile hybrid sturgeon Acipenser ruthenus ♂ × A. baeri♀, an important coldwater finfish farmed in China and other countries. Seven experimental diets (Diet A–G) containing different levels of AFB₁ (0, 1, 5, 10, 20, 40 and 80 μg kg^?1 diet) were fed to juvenile sturgeon weighing 10.53 ± 0.17 g kg^?1 to determine its effect on survival, growth, feed consumption, hematocrit, liver histology as well as muscular and hepatic toxin accumulation. The experiment lasted for 35 days and was conducted in two periods of 25 and 10 days each. No external changes or unusual behaviour was observed in the fish fed diets with AFB₁. Mortality was observed in fish fed with highest levels of AFB₁ (80 μg kg^?1– Diet G) from day 12 onwards. After 25 days, fish fed the diet of 80 μg AFB₁ kg^?1 showed significant lower survival (50 ± 5.77%) followed by those fed 40 μg AFB₁ kg^?1 diet (80 ± 5.77%) and 20 μg AFB₁ kg^?1 diet (86.66 ± 3.33%). No significant difference was observed in specific growth rate (SGR) or hepatosomatic index (HSI) between groups. Hematocrit was significantly higher in the fish fed the diet of highest AFB₁. The fish were weighed at day 25 in some treatments (Diets F and G) because of high mortality. However, feeding was continued for another 10 days to observe mortality or behavioural changes if any in the other groups. After 35 days, survival in the fish fed Diet F (40 μg AFB₁ kg^?1) was 40% and those fed Diet E (20 μg AFB₁ kg^?1) was 36.2%. Significant histopathological changes including nuclear hypertrophy, hyperchromasia, extensive biliary hyperplasia, focal hepatocyte necrosis and presence of inflammatory cells were observed in the liver of fish fed high levels of aflatoxin (40 and 80 μg kg^?1). AFB₁ accumulation in fish muscle and liver increased with increased dietary AFB₁ levels. It could be confirmed that 10 μg AFB₁ kg^?1 diet was the maximum allowable level in hybrid sturgeon diet.     

Effect of route of administration and carrier on bioavailability and kinetics of astaxanthin in Atlantic salmon Salmo salar L.

This study examined astaxanthin bioavailability and kinetics in adult Atlantic salmon Salmo salar L., following two different routes of astaxanthin administration (oral vs. intraperitoneal (i.p.) injection) using two different carriers of the pigment (gelatin vs. sesame oil). The dorsal aorta of adult Atlantic salmon (mean initial weight 950 g) was cannulated. The fish received a single dose of astaxanthin (572 μg kg^?1) in sesame oil or (514 μg kg^?1) in gelatin via the oral or i.p. route. Plasma was sampled regularly up to 72 h post oral administration and up to 510 h post i.p. injection. The astaxanthin concentration–time curves from plasma were best fit to a one‐compartment pharmacokinetic model for each of the four treatments. The gelatin carrier resulted in higher availability of astaxanthin compared to the sesame oil carrier. The bioavailability for astaxanthin in sesame oil was only 38.7% of that in gelatin by i.p. injection, and only 53.5% of that in gelatin by oral administration. Higher availability of astaxanthin was observed when i.p. injection was used compared to oral administration. The bioavailability for astaxanthin administered orally was only 12% of that by i.p. injection in sesame oil, and only 8.7% of that by i.p. injection in gelatin.