A single-dose pharmacokinetic study of oxolinic acid and vetoquinol, an oxolinic acid ester, in Atlantic halibut, Hippoglossus hippoglossus L., held in sea water at 9 °C

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 (Cl_T) was determined to be 0.044 L kg^–1 h^–1. The volume of distribution at steady state, V_d(ss), was calculated to be 3.0 L kg^–1, indicating good tissue penetration of oxolinic acid in Atlantic halibut. The peak plasma concentration (C_max) and the time to peak plasma concentration (T_max) 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 C_max and T_max 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, respectively. For resistant strains with a MIC of 1 μg mL^–1, a single oral dose of vetoquinol (25 mg kg^–1) maintained plasma levels in excess of 4 μg mL^–1 for 34 h.     

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.     

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.     

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.     

Antibacterial efficacy and pharmacokinetic evaluation of sanguinarine in common carp (Cyprinus carpio) following a single intraperitoneal administration

Sanguinarine (SA), with antimicrobial and antiparasitic activities against fish pathogens, exhibits great potential commercial use in aquaculture. However, little information on pharmacokinetics of SA restricts further application in aquaculture. In this study, pharmacokinetics of SA in common carp (Cyprinus carpio) following a single intraperitoneal administration [10 mg kg^?1 BW (body weight)] was evaluated by high‐performance liquid chromatography (HPLC). The peak concentration (C_max) of SA in kidney was 11.8 μg g^?1, which was higher than in other tissues and plasma. The terminal half‐life in fish tissue and plasma was as follows: 42.3 h (kidney) > 37.2 h (liver) > 20.1 h (gill) > 18.8 h (muscle) > 10.9 h (spleen) > 10.0 h (plasma). Additionally, we determined the bacterial loads in tissues of common carp infected with Aeromonas hydrophila after i.p. administration of SA at 0, 5, 10 and 20 mg kg^?1 BW. The results showed that i.p. administration of SA at 10 mg kg^?1 BW significantly enhanced antibacterial efficacy against A. hydrophila, where the antibacterial ratio in the gill, kidney, spleen and liver on day 5 was 95.13%, 93.33%, 90.09% and 92.82%, respectively. Overall, these results suggested the potential of SA to treat A. hydrophila infection in common carp farming industry.     

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.     

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.     

Single Intravascular and Oral Dose Pharmacokinetics of Mebendazole in Blunt Snout Bream,Megalobrama amblycephala

Mebendazole (MBZ) is a broad‐spectrum benzimidazole methylcarbamate anthelmintic used widely in animal husbandry and aquaculture. However, there is no information available on the pharmacokinetic behavior of MBZ in blunt snout bream, Megalobrama amblycephala. In this study, pharmacokinetic parameters of MBZ were estimated in blunt snout bream after intravascular (3 mg/kg body weight [BW]) and oral (20 mg/kg BW) administration. The analyses of plasma samples were performed using ultra performance liquid chromatography with ultraviolet detector. After intravascular administration, plasma concentration–time curves were best described by a two‐compartment open model. The distribution half‐life (t_1/2α), elimination half‐life (t_1/2β), and area under the concentration–time curve (AUC) of blunt snout bream were 0.1 h, 27.9 h, and 56666.0 h.µg/L, respectively. After oral administration, a one‐compartment open model with first‐order absorption best fit the plasma data. The absorption half‐life (t_1/2Ka), elimination half‐life (t_1/2Ke), peak concentration (C_max), time‐to‐peak concentration (T_max), and AUC of blunt snout bream were estimated to be 1.9 h, 34.6 h, 918.1 µg/L, 8.4 h, and 54201.4 h.µg/L, respectively. The oral bioavailability (F) was 14.3 %. The pharmacokinetics of MBZ in blunt snout bream displayed low bioavailability, relatively rapid absorption, and relatively rapid elimination.     

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.     

Enrofloxacin pharmacokinetics in Takifugu flavidus after oral administration at three salinity levels

The present study was designed to explore the pharmacokinetics of enrofloxacin in Takifugu flavidus at different salinity levels (10‰, 20‰ and 30‰). The concentrations of enrofloxacin in plasma and tissues (kidney, liver and muscle) of T. flavidus after a single oral dose of 10 mg kg^?1 were simultaneously determined using HPLC. The parameters of pharmacokinetics were calculated using non‐compartmental model based on statistic moment theory. The peak concentrations of enrofloxacin were higher and T_max values in plasma, liver and muscle tissues of T. flavidus were lower at the salinity of 20‰ and 30‰ than that of 10‰, except the kidney tissue. These demonstrated the absorption of enrofloxacin was more quickly and more quantity at the high salinity. The elimination half‐life (t_1/2z) of enrofloxacin in the plasma (45.22, 69.91 and 95.45 h) was increasing with the increase in salinity. And the t_1/2z values of enrofloxacin in liver (76.44, 44.21 and 33.48 h) and kidney (212.16, 157.43 and 35.61 h) both decline with the increase in salinity, indicating the elimination of enrofloxacin was faster in liver and kidney but slower in plasma at the high salinity. The content of enrofloxacin in liver was increasing with the increase in salinity, suggesting that salinity affects tissue distribution and metabolism in T. flavidus. In addition, the AUC_0–∞ data of enrofloxacin (kidney > plasma > liver > muscle) at different salinity levels were essentially consistent, and AUC_0–∞ data of kidney were declined with the increase in salinity, supporting that the kidney was the main organ and the role of extent of kidney on excretion was different in different salinity levels.     

Pharmacokinetics of Florfenicol after Oral Administration in Yellow Catfish,Pelteobagrus fulvidraco

The pharmacokinetics of florfenicol (FF) and its metabolite, florfenicol amine (FFA), were investigated after doses of 10 mg/kg/day were administered orally per os (p.o.) on a single day or on three consecutive days in yellow catfish, Pelteobagrus fulvidraco, raised in water temperatures of 25 C. After a single dose p.o. was administered, the apparent volume of distribution at steady state (V_dss) of FF was computed to be 2.52 L/kg. The T_max values were in the following order: liver (1.82 h) < kidney (2.26 h) < skin (6.15 h) < muscle (6.32 h) < plasma (7.25 h). These results show that FF and FFA accumulated rapidly in the kidney and liver. The t_1/2β values in plasma, muscle, skin, liver, and kidney were 9.63, 15.75, 14.44, 11.55, and 15.75 h, respectively, for FF and 21.66, 15.07, 17.33, 26.65, and 30.13 h, respectively, for FFA. After a single p.o. dose was administered on three consecutive days, the t_1/2β values of FF and FFA in skin‐on muscle were 17.12 and 13.55 h, respectively. The total concentrations of FF and FFA in skin‐on muscle 1, 3, and 5 d after the last administration were 3.39, 0.5, and 0.062 µg/g, respectively.     

肌注和口服氟苯尼考在中华鳖体内残留分析及药代动力学

研究不同给药条件下，氟苯尼考在中华鳖体内的残留及药代动力学特征。健康中华鳖160只，随机分为2组，按30 mg·kg^-1剂量分别单次肌注或口服氟苯尼考，高效液相色谱法测定中华鳖血浆和肌肉药物残留浓度，利用3P87药代动力学软件分析数据。肌注和口服时均符合一室开放模型；肌注给药的动力学方程C=16.72(e^-0.15t-e^0.52t) ，主要药代动力学参数：AUC=76.45 μg·mL^-1·h^-1，吸收半衰期（T_1/2Ka）=1.31 h，半衰期(T_1/2Ke)=4.48 h，最高血药浓度C_max=7.09 μg·L^-1；口服给药的动力学 方程为C=39.99(e^-0.19t-e^0.4t)，主要药代动力学参数：AUC=109.42 μg·mL^-1·h^-1，吸收半衰期（T_1/2Ka）=1.73 h，半衰期(T_1/2Ke)=3.63 h，最高血药浓度C_max=10.64 〗μg·L^-1。实验结果表明，氟苯尼考口服情况下，在中华鳖体内吸收快，血药浓度高，维持时间长，生物利用度高；药物在肌肉中消除缓慢。     

Pharmacokinetics of sulfamonomethoxine in tongue sole (Cynoglossus semilaevis) after intravenous and oral administration

The pharmacokinetic profiles of sulfamonomethoxine (SMM) were investigated in flatfish tongue soles in the present study. After a single injection of SMM (40 mg/kg BW) to caudal vein of tongue sole at 20 °C, plasma drug concentration versus time data were best fitted to a three-compartment model, characterized with 0.2, 5.7, and 80.4 h for the half-life (t _1/2) of fast distribution, slow distribution, and elimination, respectively. The apparent volume of distribution was 0.1 L/kg, and the body clearance was 0.03 L/h/kg. After oral administration of SMM (200 mg/kg BW) to tongue soles at 20 °C, plasma drug concentrations were best fitted to a two-compartment model, of which the mean half-life of absorption (t _1/2ka) and elimination (t _1/2β ) were 1.7 and 95.7 h, respectively. The maximal absorption concentration (C _max) was estimated as 58 mg/L at 2.5 h, and the mean systemic bioavailability (F) was 39.5 % in tongue soles after oral administration.     

Pharmacokinetics and bioavailabilities of 14C-keto-carotenoids, astaxanthin and canthaxanthin, in rainbow trout, Oncorhynchus mykiss

The pharmacokinetics and bioavailabilities of ¹⁴C‐astaxanthin and ¹⁴C‐canthaxanthin were studied in the blood of rainbow trout following intra‐arterial (i.a.) and oral (p.o.) administration. Sixteen months old 1 kg trout were cannulated in the dorsal aorta. [6,7,6′,7′‐¹⁴C]‐keto‐carotenoids were administered i.a. and p.o. at a dose of 573.5 kBq kg^?1 fish body weight for astaxanthin and 836.2 kBq kg^?1 fish body weight for canthaxanthin. After i.a. distribution, total body clearance (Cl_tot) was 17.30±20.29 mL kg^?1 of fish h^?1 for ¹⁴C‐canthaxanthin and 3.30±1.50 mL kg^?1 of fish h^?1 for ¹⁴C‐astaxanthin. The volume of distribution at steady‐state (V_ss) was 208.32±124.79 mL kg^?1 of fish and 71.84±64.15 mL kg^?1 of fish for ¹⁴C‐canthaxanthin and ¹⁴C‐astaxanthin respectively. Less than 0.4% of the administered radioactivity was recovered in urine. Radioactivity (expressed as percent of the dose) excreted in the bile of fish that received ¹⁴C‐canthaxanthin by i.a. route was 20‐fold higher than that observed for fish treated p.o. This ratio was lower for ¹⁴C‐astaxanthin (7.6‐fold). The mean keto‐carotenoid bioavailabilities calculated were 10–15% for both compounds. Findings suggest one daily astaxanthin application is preferable, while 12‐h time intervals between applications are preferable for canthaxanthin.     

Effect of dietary composition on specific dynamic action in southern catfish Silurus meridionalis Chen

The effect of dietary macronutrient composition on specific dynamic action (SDA) in southern catfish Silurus meridionalis Chen juveniles (39.0±2.8 g) was studied. A control diet (40% protein, 10% lipid and 15% carbohydrate) was the optimal dietary profile for growth in this catfish according to a previous study. Based on this, two diets were formulated by substituting protein and lipid for one another, referred to as LPHL (30% P:15% L) and HPLL (50% P:5% L), and two diets were formulated by substituting protein and carbohydrate for one another, referred to as LPHC (30% P:30% C) and HPLC (50% P:0% C). The results showed that dietary composition affected the peak metabolic rate, duration and SDA coefficient. The peak metabolic rate in the LPHC group (211.5 mgO₂ kg^?1 h^?1) was significantly lower than catfish in the control (265.2 mg O₂ kg^?1 h^?1) and the HPLC (257.7 mg O₂ kg^?1 h^?1) group. The SDA duration in the control group (26.8 h) was significantly shorter than those of the HPLL (38.0 h), LPHC (33.8 h) and HPLC (33.8 h) groups. The SDA coefficient in the LPHL group (11.1%) was significantly lower than those of the control and the other groups (13.2–15.4%). The results suggest that in southern catfish, the SDA response to dietary carbohydrate is similar to that of dietary protein, and that the SDA may not be affected solely by an increase in the amount of protein ingested, but may be influenced by interaction of other dietary components.     

A preliminary study on tailoring of fillet iodine concentrations in adult Atlantic salmon (Salmo salar L.) through dietary supplementation

The present study was performed to assess to what degree supplemented dietary iodine (I) was retained in selected tissues, including the fillet of adult Atlantic salmon (Salmo salar) reared in sea water. Atlantic salmon weighing approximately 1.5 kg were randomly assigned to three net pens per treatment and fed moist pellets (based on minced saithe and herring) supplemented with 0, 40 or 80 mg iodine (as KI) kg^?1 on dry weight basis for 150 days. The iodine concentrations in the experimental feeds were analysed to be 10, 54 and 86 mg kg^?1 dry weight, respectively. Growth, mortality and blood haemoglobin concentration (Hb) were recorded. Iodine concentrations were measured in muscle, liver and kidney after 90 and 150 days of feeding by inductively coupled plasma‐mass spectrometry. In addition, plasma thyroxine (T₄) and triiodo‐thyronine (T₃) were determined. The weight gain during the period was approximately 1 kg for all treatments. There were no mortalities, and blood Hb levels were within normal ranges. The iodine concentration in muscle, liver and kidney were all affected by the dietary iodine level, despite wide intratreatment variation. After 150 days, fillets of fish fed 10, 54 and 86 mg I kg^?1 showed mean concentrations of 0.4, 0.5 and 0.9 mg I kg^?1 wet weight, respectively, whereas the iodine concentration in the liver and the kidney increased approximately three times in the dietary groups. Similarly, plasma T₄ and T₃ showed great variation within the treatments. No significant correlations were found between individual tissue iodine concentration and thyroid hormone concentration in any of the groups at any sampling time. This preliminary feeding experiment showed that fillet iodine in adult Atlantic salmon can be increased up to 1.4 mg I kg^?1 wet weight by dietary iodine 80 times the minimum requirement for salmonids, without impacting health, performance or plasma thyroid hormone status.     

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.     

Pharmacokinetics,optimal dosages and withdrawal time of florfenicol in Asian seabass (Lates calcarifer) after oral administration via medicated feed

Asian seabass (Lates calcarifer) is an economically important fish in Asian and Australian markets, but few pharmacokinetic (PK) data of antimicrobial drugs in this species is available. The present study investigated the PK behaviour of florfenicol (FF) through medicated feed in Asian seabass cultured at 25°C. The serum and muscle/skin concentrations of FF and its metabolite florfenicol amine (FFA) were determined by the HPLC-FLD method and analysed by one-compartmental model. The optimal dosages were determined by pharmacokinetic-pharmacodynamic (PK-PD) approach and the linear regression analysis was used to determine the withdrawal time (WDT). The PK study following a single oral administration of 15 mg/kg FF via medicated feed revealed that the absorption half-life (t_1/2Ka), elimination half-life (t_1/2K), peak concentration (C_max), area under the concentration-time curve (AUC), volume of distribution (Vd/F) and clearance (CL/F) were 1.47 h, 8.07 h, 8.61 μg/ml, 146.41 h·μg/ml, 1.19 L/kg and 0.102 L/kg/h, respectively. The muscle/skin concentration-time profile was similar to that of the serum, suggesting well distribution but only a small fraction of FF was metabolized to FFA. The optimal dosage for a minimum inhibitory concentration of 2 μg/ml was calculated as 13.38 mg/kg/day. The appropriate WDT after multiple oral medications with 15 mg/kg FF once daily for 7 days was determined as 8 days. Information obtained from the current study can potentially be applied for the treatment of bacterial diseases in farming Asian seabass.     

Depletion of florfenicol amine in tilapia (Oreochromis sp.) maintained in a recirculating aquaculture system following Aquaflor®‐medicated feed therapy

Aquaflor^® [50% w w^?1 florfenicol (FFC)], is approved for use in freshwater‐reared warmwater finfish which include tilapia Oreochromis spp. in the United States to control mortality from Streptococcus iniae. The depletion of florfenicol amine (FFA), the marker residue of FFC, was evaluated after feeding FFC‐medicated feed to deliver a nominal 20 mg FFC kg^?1 BW d^?1 dose (1.33× the label use of 15 mg FFC kg^?1 BW d^?1) to Nile tilapia O. niloticus and hybrid tilapia O. niloticus × O. aureus held in a recirculating aquaculture system (RAS) at production‐scale holding densities. Florfenicol amine concentrations were determined in fillets taken from 10 fish before dosing and from 20 fish at nine time points after dosing (from 1 to 240 h post‐dosing). Water samples were assayed for FFC before, during and after the dosing period. Parameters monitored included daily feed consumption and biofilter function (levels of ammonia, nitrite and nitrate). Mean fillet FFA concentration decreased from 13.77 μg g^?1 at 1‐h post dosing to 0.39 μg g^?1 at 240‐h post dosing. Water FFC concentration decreased from a maximum of 1400 ng mL^?1 at 1 day post‐dosing to 847 ng mL^?1 at 240 h post‐dosing. There were no adverse effects noted on fish, feed consumption or biofilter function associated with FFC‐medicated feed administration to tilapia.