诺氟沙星在大黄鱼体内的药代动力学及残留研究

在试验水温(22±2)℃时,按10 mg.kg-1的剂量给大黄鱼单次口服诺氟沙星后,用高效液相色谱法测定血浆和组织中的药物浓度,研究了诺氟沙星在大黄鱼体内的代谢及消除。结果表明血药时间数据符合一级吸收二室开放模型,吸收分布迅速,但消除缓慢,半衰期(T1/2 Ka、T1/2α、T1/2β)分别为0.703 0、2.092 6、154.326 5 h,最大血药浓度为0.886 4μg.mL-1,达峰时间为2.091 4 h,药时曲线下面积(AUC)为97.803 8μg.h.mL-1。组织中肝脏的药物浓度最高,在测定的时间里各组织的药物浓度高于血浆。药物消除速度依次为:肾脏、肝脏、肌肉,消除半衰期分别为135.88、173.25、223.55 h,肌肉作为可食性组织,且消除最慢,因此选取肌肉组织作为残留检测的靶组织,以50μg.kg-1为最高残留限量,因此在本试验条件下,建议休药期不低于23 d;在治疗大黄鱼细菌性疾病时,以诺氟沙星10 mg.kg-1剂量给药,一般1 d 1次,连用2~3 d。     

诺氟沙星在大菱鲆体内药代动力学及残留消除规律

利用高效液相色谱法分别测定了单次和多次混饲口灌大菱鲆诺氟沙星(NFLX)后鱼体主要组织中的NFLX含量。通过MCP-KP药动学程序对NFLX在大菱鲆体内的药代动力学及残留消除规律进行了分析研究。结果表明,以30mg/kg的剂量单次混饲口灌大菱鲆,NFLX在大菱鲆体内的达峰时间(Tmax)为2h,血、鳃、肾脏、肝脏、肌肉的达峰浓度(Cmax)分别为:8.365、7.519、1.871、6.485和4.060μg/g;NFLX在组织中的消除半衰期(T1/2)由小到大依次为:肝脏8.18h<肌肉12.39h<鳃丝15.29h<血液23.22h<肾脏23.25h。连续5d以30mg/kg的剂量混饲口灌大菱鲆,消除半衰期(T1/2)由小到大依次为:肌肉74.88h<血液98.16h<肝脏186.43h<鳃192.12h<肾脏200.45h。以上研究表明,诺氟沙星在大菱鲆体内的吸收较为迅速,有利于疾病的预防和治疗用药。在组织中以肾脏中的残留最为显著。使用诺氟沙星进行大菱鲆疾病的预防和治疗时,至少停药30d后方可上市销售。     

盐酸土霉素在奥尼罗非鱼体内的药代动力学及残留研究

在水温(25±2)℃条件下,以15 mg/kg鱼体重的剂量给奥尼罗非鱼单次口灌盐酸土霉素,采用高效液相色谱法测定血浆和肌肉组织中的药物浓度,研究盐酸土霉素在奥尼罗非鱼体内的代谢及消除规律。结果显示:血药时间数据符合一级吸收二室开放模型,半衰期(T1/2Ka、T1/2α、T1/2β)分别为4.79、4.10、45.20 h,最大血药浓度为1.50μg/m L,达峰时间为7.30 h,药时曲线下面积(AUC)为42.35μg·h/m L。肌肉作为可食性组织,选取肌肉组织作为残留检测的靶组织,以0.1 mg/kg为最高残留限量,在本试验条件下,建议休药期不低于10 d。     

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。     

诺氟沙星在中华鳖体内的药代动力学研究

用反相高效液相色谱法测定了中华鳖口服诺氟沙星后体内的血液浓度，结果显示，其口服给药的血荭浓度时间曲线符合单室模型一级吸收。其主要药代动力学参数为：吸收半衰期为２．３０ｈ，时滞为０．１４ｈ，达峰时间为４．５８ｈ，峰浓度为３．２７μｇ／ｍＬ消除半衰期为４．２４ｎ，统计短分析其平均滞留时间为１０．６６ｈ。     

溴氰菊酯在欧洲鳗鲡体内药代动力学研究

在试验水温(25±1)℃时,按100μg·L-1的剂量给欧洲鳗鲡药浴溴氰菊酯36h后,采用气相色谱法测定血浆和肌肉中的药物浓度,研究了溴氰菊酯在欧洲鳗鲡体内的代谢及消除规律.采用DAS自动化药动学分析程序对数据进行分析.结果表明:欧洲鳗鲡血浆和肌肉中溴氰菊酯经时过程均符合一级吸收一室开放模型,血浆中主要药动学参数为:T1/2k为148.296h,Cmax为18.446μg·L-1,Tmax为14.7h.肌肉中主要药动学参数为:T1/2k为386.912h,Cmax为44.291μg·kg-1,Tmax为49.6h.肌肉作为可食性组织,且消除较慢,因此选取肌肉组织作为残留检测的靶组织,以10μg·kg-1为最高残留限量,在本试验条件下,建议休药期不低于9d.     

伊维菌素在鲫体内的药代动力学

以0.4 mg/kg的给药剂量进行口灌和肌肉注射给药,研究伊维菌素(IVM)在鲫体内的药代动力学。两种给药方式下,鲫组织中的IVM药—时曲线大都呈现多峰现象。肌肉注射给药后,药动学统计矩参数为Cmax=0.445 mg/L、Tmax=48 h、t1/2z=524.2 h、MRT(0-∞)=788 h、AUC(0-∞)=289.2(mg/L).h;口灌给药后,药动学统计矩参数为Cmax=0.264 mg/L、Tmax=8 h、t1/2z=153.9h、MRT(0-∞)=269.78 h、AUC(0-∞)=83.77(mg/L).h。两种给药方式相比,口灌组鲫对药物的吸收和清除均较快,而肌肉注射组鲫各组织中的药物浓度高,AUC值也较大。两种给药方式下,IVM在鲫各组织中AUC(0-600)值呈现相同的排列顺序,由大到小分别为性腺、血液、肾脏、肝胰脏、肌肉。IVM在鲫性腺和肾脏中均具有一定的蓄积作用,其主要表现为药物浓度高,MRT值大,且清除率低于血药的清除率,其中卵巢的积蓄作用最为明显。25℃的水温条件下,肌肉注射给药后,鲫休药期应不低于25 d;口灌给药后,鲫的休药期应不低于15 d。休药期与水温条件和给药剂量有关,因此在养殖生产过程中的休药期要根据实际情况适当调整。     

达氟沙星在健康大菱鲆体内的药代动力学研究

在水温16±0.6℃条件下,以20mg/kg鱼体重剂量对健康大菱鲆静脉注射和口服达氟沙星,利用高效液相色谱法测定96h内血浆和组织中的达氟沙星含量.DAS 2.0自动药动学软件分析表明,静注给药时,达氟沙星的血药经时过程符合零级吸收二室开放模型,表达方程式为C静注-45.74le-1.927t+7.332e-0.019t,消除半衰期(t1/2β)和药时曲线下面积(AUC0-t)分别为36.336h和431.981h·μg/ml;口服给药时,达氟沙星的血药经时过程符合一级吸收二室开放模型,表达方程式为C中服-6.796e-0.05t+3.135e-0.005t-9.931e-0.011t,12h时血药浓度达到最大值(Cmax)5.312μg/ml,消除半衰期、药时曲线下面积和表观分布容积(Vd)分别为129.228h、284.915 h·μg/ml和2.986 L/kg;口服达氟沙星的生物利用度(F)为65.96%,肝脏和肾脏内的药物浓度较高,与血药浓度相似,而肌肉内较低.根据达氟沙星在大菱鲆体内的药代动力学特点及其对主要致病菌的体外抑菌参数指标,提出了口服给药方案:按12.17mg/kg体重/次,1日1次.     

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.     

Gill net selectivity for perch (Perca fluviatilis) in the Szczecin Lagoon, Poland

This paper presents the scientific basis for changes in the minimum mesh size in gill nets, from 28 to 30 mm, introduced by fishery management in Poland to limit the catch of undersized perch (those less than 17 cm total length). Experimental fishing with six different mesh sizes was performed in accordance with commercial fisheries practice. A bi-normal selection curve was fitted to the data by including the between-set variation in the model. The locations of the primary and secondary modes of the bi-normal curve on the transformed length scale (length/mesh) were estimated to be 6.95 and 7.41, respectively. The results indicated that a minimum mesh size in gill nets of 28 mm should be sufficient to ensure a low level of discards as well as protecting the interests of fishermen.     

诺氟沙星在牙鲆体内的残留及消除规律研究

首次报道了诺氟沙星(Norfloxacin，NFLX)在牙鲆体内的残留及消除规律并建立了组织中NFLX的分离提取及检测方法。以30mg／kg剂量连续5d口服灌胃给药，取血液、肌肉、肝脏、肾脏、鳃5种组织，组织中药物先加入pH7．4磷酸盐缓冲液匀浆，再用乙腈振荡提取，反相高效液相色谱法测定其中诺氟沙星的残留浓度，此方法平均回收率71．37％～82．13％，最低检测限达0．005μg/ml。残留研究结果表明，诺氟沙星在5种组织中消除速率快慢不一，肾脏及鳃等非食用组织为诺氟沙星残留的靶组织。若规定可食用组织中的诺氟沙星最大残留限量为50μg／kg，在本实验条件下，建议临床休药期为10d。     

单剂量口灌阿维菌素在草鱼体内的药动学及残留研究

按0.1 mg/kg的剂量给草鱼(Ctenopharyngodon idellus)灌服阿维菌素,用高效液相色谱法检测用药后不同时间的血浆、肌肉和肝脏中的药物浓度,然后用3P97药代动力学软件处理药时数据,对药物在草鱼体内药动学及组织残留进行研究.结果表明:单剂量口灌阿维菌素在草鱼血浆中主要药动学参数为:AUC 1 6...     

Depletion of isoeugenol residues from the fillet tissue of AQUI-S™ exposed rainbow trout (Oncorhynchus mykiss)

There is a critical need in U.S. public aquaculture and fishery management for an approved sedative that allows for the immediate release of fish after sedation. AQUI-S^TM is a fish anesthetic/sedative approved for use in several countries and until recently was being developed in the U.S. as a sedative for immediate release of fish after sedation. The U.S. National Toxicology Program reported that isoeugenol (the active ingredient in AQUI-S^TM) exposed male mice showed clear evidence of carcinogenicity, therefore efforts within the U.S. Department of Interior to develop AQUI-S^TM as a sedative that allows for immediate release ceased. Despite the ruling, AQUI-S^TM still has the potential to be approved as an anesthetic with a short withdrawal time. Among the data required to gain approval for use in the U.S. are data describing the composition and depletion of all AQUI-S^TM residues from fish fillet tissue. A total residue depletion study for AQUI-S^TM was conducted by exposing market-sized rainbow trout, Oncorhynchus mykiss (mean weight, 502.7 ± 54 g; s.d.) to 8.9 mg/L of ¹⁴C-[URL]-isoeugenol for 60 min in 17 °C water. The ¹⁴C-[URL]-isoeugenol was mixed with a surfactant resulting in a mixture that mimicked AQUI-S^TM. Groups of fish (n = 6) were sampled immediately after the exposure (0-h sample group) and at 0.5, 1, 2, and 4 h thereafter. Total isoeugenol-equivalent residue concentrations in the fillet tissue were determined by oxidizing triplicate subsamples of homogenized skin-on fillet tissue from each fish to ¹⁴CO₂ and enumerating the radioactivity by static liquid scintillation counting. Isoeugenol concentrations in fillet tissue were determined by extracting homogenized fillet tissue with solvents and determining the isoeugenol concentrations in the extracts with high performance liquid chromatography techniques. The mean total isoeugenol-equivalent residue concentrations in the 0, 0.5, 1, 2, and 4-h sample groups were 55.4, 32.0, 19.8, 11.3, and 4.9 µg/g, respectively. The primary chemical residue in fillet tissue from all exposed fish was isoeugenol. The mean isoeugenol concentrations in the 0, 0.5, 1, 2, and 4-h sample groups were 48.9, 26.5, 15.3, 7.2, and 2.2 µg/g, respectively. The percents of the total radioactivity classified as isoeugenol in the 0, 0.5, 1, 2, and 4-h tissue extracts were 95, 73, 73, 64, and 48%, respectively.     

Environmental determinants of perch (Perca fluviatilis) growth in gravel pit lakes and the relative performance of simple versus complex ecological predictors

Growth of fish is an important contributor to individual fitness as well as fish production. Explaining and predicting growth variation across populations is thus important from fundamental and applied perspectives, which requires knowledge about the ecological factors involved in shaping growth. To that end, we estimated environment-dependent von Bertalanffy growth models for 13 gravel pit lake populations of Eurasian perch (Perca fluviatilis) from north-western Germany. To identify the main drivers of perch growth, we evaluated the performance of 16 different biotic or abiotic lake variables in explaining growth variation among lakes. In addition, we compared growth predictions from the best-performing model incorporating “complex” variables that require intensive sampling effort, with a model using only “simple”, easily measurable lake variables (e.g. shoreline development factor). The derivation of a simple model aimed at future applications in typically data-poor inland fisheries, predicting expected growth potential from easily measurable lake variables. A model combining metabolic biomass of predators, maximum depth and shoreline development factor performed best in predicting perch growth variation across gravel pits. All three parameters in this model were positively related to perch growth. The best-performing simple model consisted only of the shoreline development factor. Length-at-age predictions from both models were largely identical, highlighting the utility of shoreline development factor in approximating growth potential of perch in gravel pits similar to our study lakes. Our results can be used to inform fisheries management and restoration efforts at existing or newly excavated gravel pit lakes.     

Salinity tolerance of cultured Eurasian perch, Perca fluviatilis L.: Effects on growth and on survival as a function of temperature

Eurasian perch is generally only considered to be a candidate for freshwater aquaculture even though wild populations are found in estuarine and brackish water habitats. Little knowledge exists on two issues a) the effect of temperature on the salinity tolerance of perch and b) the long-term effects of brackish water on their overall growth performance. The present study addresses these two questions.

Firstly, the effect of temperature (12, 15, 20 and 25°C) on perch survival of a salinity challenge at either 13 or 18‰ was determined. Survival was unaffected by 13‰ at the two lowest temperatures whereas higher temperature and higher salinities had a dramatic detrimental effect (at 25°C, 50% mortality was reach at 62h and 39h for 13‰ and 18‰, respectively). Secondly, we examined the effect of salinity on growth, which was assessed by measuring standard length and body weight at regular intervals for 130days. In addition, Specific growth rate (SGR), Fulton's condition factor (K) and food conversion ratio (FCR) were also calculated as was the effect of salinity on plasma osmolality, blood ion content (Na⁺, Cl⁻, K⁺) and muscle water content at the termination of the experiment. The optimum growth for this study was seen in the lowest salinities at 0 and 4‰. Surprisingly, even small increases in salinity were detrimental to perch growth. At 10‰, growth in terms of body weight was reduced by about 50% after 130days compared to perch reared in freshwater.

Interest in brackish water production of perch would be most likely served best by selecting a strain of perch that is adapted to saline conditions, as found in the lower Baltic region. Further studies are required to understand the potential for brackish water perch production.     

盐酸沙拉沙星在锦鲤体内的组织残留研究

健康锦鲤以15 mg/kg的单剂量肌肉注射给药,采用反相高效液相色谱法测定取给药后不同时间的肌肉、肾脏和肝胰脏中盐酸沙拉沙星的质量浓度,用MCPKP软件进行数据处理和分析。结果表明,盐酸沙拉沙星在肾脏、肝胰脏和肌肉组织中的代谢动力学特征不一。肌肉的代谢动力学模型为一级吸收二室开放模型,在肝脏和肾脏组织中代谢动力学模型为一级吸收一室开放模型。数据经回归处理得到3种组织的消除半衰期T1/2肌肉为55.44 h;T1/2肝脏为13.0755 h;T1/2肾脏为33 h。通过休药期公式计算各组织的理论休药期为:肌肉:11.0 d;肝脏:6.6 d;肾脏:9.5 d。以残留量高、消除最慢的组织作为残留分析的靶组织,建议锦鲤以肌肉为残留靶组织,在25℃的条件下,肌肉以10μg/kg为最高残留限量,建议休药期为11 d。     

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。