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,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.     

Pharmacokinetics and bioavailability of oxytetracycline in vannamei shrimp (Penaeus vannamei) and the effect of processing on the residues in muscle and shell

The present study examined the pharmacokinetics and bioavailability of oxytetracycline (OTC) in vannamei shrimp (Penaeus vannamei) after intra-sinus (10 mg/kg) and oral (10 and 50 mg/kg) administration and also investigated the net changes of OTC residues in the shrimp after the thermal, acid and alkaline processing methods. The hemolymph concentrations of OTC after intra-sinus dosing were best described by a two-compartment open model. The oral bioavailability was found to be 48.2 and 43.6% at doses of 10 and 50 mg OTC/kg, respectively. The peak hemolymph concentrations after 10 and 50 mg OTC/kg doses were 3.37 and 17.4 μg/ml; the times to peak hemolymph concentrations were 7 and 10 h. The elimination half-lives were found to be 15.0 and 11.5 h for the low and high dose, respectively. The residual OTC was rapidly eliminated from muscle with the elimination half-life value of 19.4 and 15.4 h, respectively, for the groups treated with doses of 10 and 50 mg/kg. The residual OTC levels in the muscle fell below the MRL (0.2 μg/g) at 72 and 96-h post-dosing at dose levels of 10 or 50 mg/kg, respectively. Residual OTC levels in muscle and shell were approximately 20–50% lower in the thermal treatment such as boiling, baking and frying. By the acid treatment, OTC residues were reduced to >80%, while those were reduced to around 30% by alkaline treatment.     

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.     

Molecular cloning of vitellogenin cDNA in rockfish (Sebastes schlegeli) and effects of estrogenic substances on its gene expression

In this study, we have cloned a partial cDNA of 620 bases encoding a vitellogenin gene of rockfish (rfVTG), Sebastes schlegeli. The expression levels of rfVTG mRNA increased 48 h after the 4-nonylphenol (NP) treatment (10 mg/kg BW) in both sexes. On the other hand, the mRNA levels of rfVTG increased 48 h in males and 12 h in females after injection when higher dose (25 mg/kg BW) of 4-NP was applied. It suggested that 4-NP induced VTG gene expression in both male and female immature rockfish. Therefore, the cloned rfVTG cDNA in this study can be used as a tool for monitoring endocrine disruptors in rockfish.     

Tissue distribution and depletion of sarafloxacin hydrochloride after in feed administration in gilthead seabream (Sparus aurata L.)

Tissue distribution and depletion of sarafloxacin was studied in gilthead seabream, under experimental field conditions at 25 and 18 °C, after in-feed administration of sarafloxacin hydrochloride for 5 days (10 mg/kg body weight/day). Ten fish per sampling point were examined during and after treatment. Muscle plus skin (n=10), liver, kidney and vertebra (pooled) were collected and analyzed by HPLC. Sarafloxacin concentrations in these tissues increased during the medication period, and then decreased rapidly. The highest sarafloxacin concentrations were recorded in liver (335.2 and 49.8 μg/g at 25 and 18 °C, respectively). In muscle plus skin, sarafloxacin concentrations were 193.0 and 42.0 μg/kg at 25 and 18 °C, respectively. Sarafloxacin residues were eliminated rapidly; at 36 h post treatment, the levels in muscle plus skin were 10.2 and 8.5 μg/kg at 25 and 18 °C, respectively. Elimination half-lives (t_1/2) were 17.8 and 32.5 h at 25 and 18 °C, respectively. Withdrawal period for the Maximum Residue Limit (MRL) of 30 μg/kg sarafloxacin in muscle plus skin (95% tolerance limit) at 25 °C was 42.2 h. The slow elimination from vertebra, relative to other tissues, suggests that vertebra behaves as a reservoir in gilthead seabream.     

Effects of dietary selenium of organic form against lead toxicity on the antioxidant system in Cyprinus carpio

In this study was evaluated potential protective effect of organic selenium (Se) on heavy metal stress induced by lead (Pb) in Cyprinus carpio. For this reason, C. carpio was exposed to sublethal concentration of Pb (1.5 mg/L Pb(NO₃)₂) for 14 days. The fish were fed a basal (control; measured 0.55 mg/kg Se) diet or a basal diet supplemented with 2.50 mg/kg (measured 2.92 mg/kg Se) organic Se (Sel-Plex^®) during the experiment period. The variations in glutathione peroxidase (GSH-Px), glutathione S-transferase (GST) activities, and levels of reduced glutathione (GSH) with malondialdehyde (MDA) in liver and brain tissues of C. carpio were investigated in experimental groups. GSH levels in liver and brain tissues were significantly decreased by exposure to Pb. GST activity was significantly increased (p < 0.05) in liver tissue, but decreased in brain of treated fish by exposure to Pb. Also, GSH-Px activity was significantly increased in liver tissue, but decreased in brain of Pb-treated fish. Levels of MDA were increased in liver and brain of Pb-treated fish. The organic Se treatment for Pb-intoxicated animals improved activities of GSH-Px, GST and levels of MDA within normal limits. Supplemented Se could be able to improve Pb-induced oxidative stress by decreasing lipid peroxidation and regulating antioxidant defense system in tissues.     

Pharmacokinetics of chloramphenicol in carp (Cyprinus carpio L.) after drug administration

Chloramphenicol (CAP) is a banned substance in fish farming; yet, residues are sometimes detected in farmed fish products. Therefore, it is important that tissue distribution and elimination rates of CAP are measured to allow monitoring of fish farms. The tissue distribution and residue of CAP in carp (Cyprinus carpio L.) after muscle injection was investigated. Chloramphenicol concentrations were determined using high‐performance liquid chromatography. Pharmacokinetics were used for the studies of CAP residue and the results showed that the CAP was easily assimilated in the liver, serum and gill, with the absorption rates of 6383, 3.02 and 1.39 h^?1, respectively, following a single‐dose injection of 80 mg kg bw^?1. The elimination half‐lives (t_1/2) were 22.28, 15.47, 14.87, 9.28 and 5.32 h for the liver, serum, gill, muscle and kidney respectively. The t_1/2 after 5 days of multi‐doses of repeated CAP injection with 40 mg kg bw^?1 was 1.09, 0.887, 0.872, 0.476 and 0.617 days for the five tissues respectively. The results validated that CAP in the liver, serum and gill could be markers for CAP residue analysis.     

三聚氰胺在斑点叉尾鮰体内的残留及代谢规律研究

(21±1)℃水温条件下,研究了三聚氰胺在斑点叉尾鮰(Ictalurus punctatus)体内的残留消除规律。结果显示:血浆中药时数据符合有吸收一室开放模型,动力学方程为:C=3.952660(e-0.027279t-e-0.127279t),吸收半衰期(T1/2kα)为5.4469 h,消除半衰期(T1/2ke)为25.4093 h,达峰时间(Tp)为15.4045 h,达峰浓度(Cmax)为20.3985 mg/L,表观分布容积(Vd)为2.5763(mg/kg)/(mg/L)。肌肉、肝、肾中吸收半衰期(T1/2kα)分别为3.5582、4.1884、5.4397 h,消除半衰期(T1/2ke)为50.8081、23.3504、23.7242 h,达峰时间(Tp)为14.6766、12.6524、14.9967 h,达峰浓度(Cmax)为7.6449、22.9249、40.6047 mg/L,表观分布容积(Vd)为8.5657、2.3970、1.2712(mg/kg)/(mg/L)。结果表明:药物在体内吸收迅速,药物浓度较高,分布广泛,消除较为缓慢。以80 mg/kg剂量混饲口灌3 d后,各组织中三聚氰胺含量总体呈现肾脏>肝脏>肌肉。停止灌药后第5天肌肉中及第7天肝脏和肾脏组织中三聚氰胺含量低于我国(2008)卫生部公布的乳制品及含乳食品中三聚氰胺临时管理限量值和欧盟对中国进口产品设定了三聚氰胺的最大残留限2.5 mg/kg。     

Effect of water hardness on peracetic acid toxicity to zebrafish, Danio rerio, embryos

The use of peracetic acid (PAA) in aquaculture has been suggested as an alternative therapeutic agent. Few data are available concerning fish toxicity by PAA or factors that modify this toxicity. The aim of this study was to investigate the influence of water hardness on the acute toxicity of PAA products to embryos of zebrafish (Danio rerio). Embryos were exposed to PAA ranging from 0 to 9 mg/L in low-hardness (1.4 °dH or 25 mg/L hardness as CaCO₃), medium-hardness (14 °dH or 250 mg/L hardness as CaCO₃) and high-hardness (140 °dH or 2,500 mg/L hardness as CaCO₃) waters. The lowest LC50 value was 2.24 mg/L PAA in the low-hardness water, and the highest LC50 value was 7.14 mg/L PAA in the high-hardness water. Toxicity of PAA to embryos was found to be negatively correlated with water hardness. The pH decreased with increasing concentrations of PAA, and the test waters were observed to become more acidic in low hardness. In conclusion, aquaculturists using PAA should pay attention to water hardness to avoid acidosis.     

复方磺胺嘧啶口灌给药在拟穴青蟹(Scylla paramamosain)体内药动学和组织分布与消除

研究了水温为(27±1)℃、盐度为10条件下,单剂量(100 mg/kg)口灌给药复方磺胺嘧啶(磺胺嘧啶SD:甲氧苄啶TMP=5:1)后,SD和TMP在拟穴青蟹(Scylla paramamosain)体内的药动学以及在肌肉、肝胰腺和鳃组织中的分布和消除规律.结果显示,拟穴青蟹口灌复方磺胺嘧啶后,血淋巴中SD和TMP药物浓度-时间关系曲线均符合一级吸收二室模型,SD和TMP的峰浓度(Cmax)分别为49.56 mg/L和2.79 mg/L,药时曲线下面积(AUC)分别为1417.6 mg/L.h和82.7 mg/L·h;肝胰腺是SD和TMP峰浓度最高的组织,其Cmax分别为59.36 mg/kg和74.82 mg/kg.由此可见,大量TMP蓄积在肝胰腺中,进入血液循环的TMP很少.在鳃组织中,SD和TMP的Cmax分别为51.89 mg/kg和42.58 mg/kg,消除半衰期分别为23.28 h和25.29 h;鳃组织中药物浓度比较高,且消除速度较快,推测其在药物代谢中承担着消除功能.在肌肉中,SD和TMP的Cmax分别为44.95 mg/kg和10.09 mg/kg,消除半衰期分别为25.09 h和35.08 h.以0.1 mg/kg和0.05 mg/kg分别为SD和TMP的最高残留限量(MRL),95％置信区间,推算SD和TMP在拟穴青蟹肌肉中的理论休药期分别为290.6 h和302.8 h,在肝胰腺中分别为340.4 h和377.0 h.     

Involvement of Gonadotropin-Releasing Hormone in Thyroxine Release in Three different forms of Teleost Fish: Barfin Founder, Masu Salmon and Goldfish

Effects of gonadotropin-releasing hormone (GnRH) on thyroxine (T₄) release in vivo and in vitro were studied in barfin flounder Verasper moseri, masu salmon Oncorhynchus masou and goldfish Carassius auratus. Seabream GnRH (sbGnRH) at a dose of 200 ng/50 g body weight (BW) significantly increased plasma T₄ levels 1 h after the in vivo injection in the barfin flounder, but thereafter the levels normalized. Salmon GnRH (sGnRH) significantly increased plasma T₄ levels l h after the injection with a significant return to initial levels in male masu salmon and male goldfish. In contrast, sGnRH and cGnRH-II in barfin flounder, and cGnRH-II in male masu salmon and male goldfish were not effective in stimulating T₄ release. To clarify direct involvement of GnRH in T₄ release, dissected lower jaw including scattered thyroid follicles was incubated with sbGnRH (1 μg/well) in barfin flounder, and with two doses (0.1 and 1 μg/well) of sGnRH in masu salmon and goldfish in vitro. T₄ concentrations of control were stable during 24 h. Incubation of lower jaw with high dose (1 μg/well) of GnRH significantly (P<0.05) increased T₄ concentrations of incubation medium at 1 h in all experimental fishes. These results indicate that direct stimulation of T₄ secretion by GnRH occurs widely in teleost fish.     

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.     

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%.     

A toxicity bioassay study concerning the effect of un-ionized ammonia on the mucus cells response originating from the gills of zebrafish Danio rerio

Ammonia is one of the most common and pervasive pollutants in the aquatic habitat affecting the health of aquatic animals. It affects the number and morphology of mucus producing cells, resulting in excessive and irregular secretion and alterations in quantity of mucus, which can lead to complications in fish health. A toxicity test on the mucus cells localized on the gills (primary lamellae) and inner operculum epithelial lining of zebrafish Danio rerio at different periods of exposure (24, 48 and 72 h) followed by recovery periods was studied using histopathology, scanning electron microscopy and anterior gradient 2 homologue (agr2) gene expression techniques. Fish samples subjected to low, medium and high external toxic ammonia concentrations (L: 17.21 mg/l, M: 25.81 mg/l and H: 38.91 mg/l NH₃-N) were observed to display a higher mucus layer production and active secretion compared with the control. Gill cellular alterations were more severe at 48 and 72 h. A high expression of agr2 was detected at 48 h (L and M) recovery periods and a (H) exposure and recovery period indicating an increase in quantity in newly proliferated alcian blue stained mucus cells and excessive secretion observed by histopathology. Such expression decreased at 72 h resulting in a decrease in mucus cell density and secretion.     

Ammonia and nitrite toxicity to false clownfish <Emphasis Type="Italic">Amphiprion ocellaris</Emphasis>

False clownfish, Amphiprion ocellaris, is one of the most commercialized fish species in the world, highly produced to supply the aquarium market. The high stocking densities used to maximize fish production can increase ammonia and nitrite to toxic levels. In this study, A. ocellaris juveniles (1.20 ± 0.34 g) were exposed to six concentrations of ammonia ranged from 0.23 to 1.63 mg/L NH₃-N and eight concentrations of nitrite (26.3–202.2 mg/L NO₂ ^?-N). The LC₅₀- 24, LC₅₀-48, LC₅₀-72 and LC₅₀-96 h were estimated to be 1.06, 0.83, 0.75 and 0.75 mg/L for NH₃-N and 188.3, 151.01, 124.1 and 108.8 mg/L for NO₂ ^?-N. Analysis of gill lesions caused by sublethal concentrations of these nitrogenous compounds showed that both nitrogenous compounds induced tissue lesions such as hyperplasia of epithelium cells, hypertrophy of chloride cells and lamellar lifting to all concentrations tested. However, histopathological alterations were more conspicuous accordingly the increase of ammonia or nitrite in fish exposed to 0.57 mg/L NH₃-N or 100 mg/L NO₂ ^?-N. Based on our results, we recommend to avoid concentrations higher than 0.57 mg/L of NH₃-N and 25 mg/L of NO₂-N in water.     

Changes in growth characteristics of the small abalone Haliotis diversicolor (Reeve, 1846) after one decade in a closed culture system: a comparison with wild populations

Small abalone Haliotis diversicolor (Reeve, 1846) is one of the smallest commercial abalone in the world. The successful application of artificial propagation and mass seed production techniques since the 1980s have resulted in the establishment of well-developed culture systems for small abalone in Taiwan. In the study reported here, we estimated the growth of a population of small abalone after a decade in a closed culture system and its growth characteristics with those of wild populations reported in previous studies. The von Bertalanffy growth equations of the shell length (L) and body weight (W) of cultured abalone were L _t  = 71.73 (1 ? e^{?0.84 (t?0.16)}) and W _t  = 47.70 (1 ? e^{?0.84 (t?0.16)})^3.180, respectively. The instantaneous rate of change for weight had an inflection point at the age of 1.54 years, indicating that cultured abalones reach their apex of body growth around this age. Compared with the wild populations, the cultured population exhibits a significantly smaller maximal shell length (L _∞) and a significantly larger growth coefficient (k). Based on our results, it appears that the artificial culture of generations of small albalone for one decade or more in a closed system could be one of the major factors causing the observed minimization of size in the cultured abalone; this may be an adaptation in which growth is traded off for the larger k.     

The Complete Analysis of the Distribution Kinetics of the Oxytetracycline Antibiotic in the Exoskeleton of Farmed Pacific White Shrimp,Litopenaeus vannamei

Oxytetracycline (OTC) in shrimp shells may be dispersed to the environment as shrimp shred old cuticle in growout ponds. The study aims to assess the kinetics of OTC accumulated in shrimp shell. Sub‐adult male Litopenaeus vannamei in the C–D₀ molting stage, were force fed with medicated feeds at various accurate dose levels that included 50, 500 and 1000 mg/kg‐body weight (BW). In addition to hemolymph, hepatopancreas and muscle were serially collected for 50 mg/kg‐BW‐dose group while cuticle was sampled for higher dose levels. All were assayed for OTC by a validated high‐performance liquid chromatography (HPLC) method. Mineral contents in shell samples of 500 mg/kg‐BW‐dose were also determined. The bioavailability markedly decreased with increasing dose due to incomplete dissolution and/or mild dysfunction in absorption. Administered doses, 2.69 and 2.25%, ended up in the shell after dosing with 500 and 1000 mg/kg‐BW, respectively. OTC data after a dose of 50 mg/kg‐BW was fitted into a three‐compartment model with an added shell compartment with r² of 0.9920. The model was successfully extrapolated to predict OTC distribution in shell at higher doses. In addition, there was evidence that OTC may disturb the biomineralization process via complex formation with calcium and magnesium lowering the exoskeleton mineral contents.