喹乙醇在肉鸡体内的组织动力学与残留的研究

研究了喹乙醇在肉鸡体内的组织动力学过程及在组织中的残留。并对血药和组织药物浓度进行动态相关分析。结果表明,药物按一级速率过程从组织中消除,药物在心、肝、肾、肌肉各组织中的半衰期分别为1.96、2.89、3.11、1.77小时。药物在各组织中的残留时间以肾脏最长、肌肉最短。     

喹乙醇在鸡体内的药物动力学及组织浓度研究

本文对24只健康石岐杂中鸡单剂量内服(30mg/kg)和静注(20mg/kg)喹乙醇作了药动学分析,对32只健康石岐杂中鸡单剂量内服喹乙醇(30mg/kg)作了组织浓度测定。用高效液相色谱法测定不同时间血浆和组织的药物浓度。喹乙醇静注给药后的血药浓度——时间数据用房室分析法、内服给药后的血药浓度——时间数据用统计矩理论非房室分析法处理。经计算所得的主要动力学参数如下,内服:t1/2 ka 0.64±0.10h,t1/2 ke 1.25±0.06h,AUC_(po) 68.84±3.12mg/L·h;静注:t1/2α 0.27±0.02h,t1/2β 1.72±0.03h,Vd 0.56±0.05L/kg,CL_B 0.23±0.01L/kg/h,AUC_(iv) 87.20±1.58mg/L·h。生物利用度F为52.99±2.32％。组织浓度测定结果表明,喹乙醇在肌肉、肝、肾、脾、肺的浓度较低,给药后24小时,这五种组织中喹乙醇的残留已低于检测限(0.2μg/g)。喹乙醇在鸡体内的吸收、分布、消除均迅速。     

喹乙醇在肉鸡体内的代谢动力学研究

本文选用高效液相色谱(HPLC)法为定量手段研究了喹乙醇在肉鸡体内的代谢动力学过程。口服喹乙醇后,肉鸡血清药物浓度——时间曲线符合开放式二室模型。其药动学参数,药物的分布相半衰期(t1/2α)为1.56(hr),消除相半衰期(t1/2β)为2.53(hr),曲线下面积(Auc)为218.7,达峰时间为1.55(hr)。     

喹乙醇在动物血浆与组织间残留分布规律研究及相关性分析

试验采用高效液相色谱分析法,对饲喂含有不同浓度喹乙醇饲料(75mg/kg、100mg/kg、125mg/kg)的猪体组织(肝脏、肾脏、肌肉)和血浆中喹乙醇含量进行检测,分析喹乙醇在猪体内的残留分布,探讨喹乙醇在血浆中的含量与猪体内组织的残留含量的相关性。结果表明:饲料中喹乙醇添加量与组织和血浆中残留量均呈线性相关关系;同一浓度的喹乙醇添加量在猪组织和血浆中的残留量分布:肝脏>肾脏>肌肉>血浆;建立的血浆与组织间残留量的回归方程具有较高的可靠性。     

喹乙醇在鲫体内消除规律的研究

报道了鲫单剂量口灌50mg／kg喹乙醇在血浆、肌肉和肝胰脏中消除规律的研究。用乙腈-乙酸乙酯（1／1：V/V）提取组织中的喹乙醇,血浆中喹乙醇用3％的三氯乙酸沉淀蛋白,乙酸乙酯和磷酸盐缓冲液提取喹乙醇代谢物3-甲基喹嗯啉-2-羧酸,超高效液相色谱串联质谱法测定血浆及组织中喹乙醇及其代谢物的浓度。鲫单剂量口灌喹乙醇50mg／kg后,在血浆、肌肉和肝胰脏中的喹乙醇随着时间的延长呈现不同浓度的降解趋势。喹乙醇在血浆中的消除需要4d,在肌肉和肝胰脏中需要7d;喹乙醇的代谢物3-甲基喹嗯啉-2-羧酸在鲫体内消除比较缓慢,肌肉中需要15d,肝胰脏中需要20d。     

喹乙醇在鸡组织的消除及残留研究

本文报道鸡多次内服（３０ｍｇ／ｋｇ，每隔１２ｈ１次，连用６次）及单剂量内服（１２０ｍｇ／ｋｇ）喹乙醇在肝、肾、肌肉及脂肪４种组织中的消除及残留的研究。用乙睛－乙酸乙酯（３／２，Ｖ／Ｖ）提取组织中的药物，反相高效液相色谱法测定组织中喹乙醇的浓度。色谱条件：Ｃ＿（１８）－ＯＤＳ柱（２５ｃｍ×４．６ｃｍ）；流动相为甲醇－水（１５／８５，Ｖ／Ｖ）；流速１．０ｍ／ｍｉｎ，紫外检测波长２６０ｎｍ。鸡多次内服喹乙醇，于第６次给药后在肝、肾、肌肉及脂肪中药物的消除半衰期分别是４．３２、４．５４、３．３１及３．０３ｈ。若规定组织中喹乙醇的最高残留限量０．００１ｍｇ？ｋｇ为可食用，则休药期应为２．５ｄ。内服单剂量喹乙醇（１２０ｍｇ／ｋｇ）后在肝、肾、肌肉及脂肪中药物的消除半衰期分别是１６．１６、１５．１９、１２．３７及１１．００ｈ，若规定食用组织中喹乙醇的最高残留限量为０．００１ｍｇ／ｋｇ，则休药期应为８．５６。结果表明，鸡内服中毒剂量的喹乙醇（１２０ｍｇ／ｋｇ）显著减慢其在体内的消除，而延长在组织中的消除半衰期及残留时间。     

三聚氰胺在中华鳖组织中的代谢动力学研究

应用液相色谱-串联质谱监测技术研究了三聚氰胺药饵多次给药后在中华鳖体内的药物代谢动力学。结果表明,中华鳖血液、肝脏、肌肉中三聚氰胺浓度分别在8、4、2h时达到高峰;最高峰时血液、肝脏、肌肉中药物质量浓度平均分别为16.98、16.79和12.05mg/kg。在血液、肝脏和肌肉组织中三聚氰胺浓度的t1/2（ke）分别为24.11、107.75和36.49h。三聚氰胺在血液、肝脏、肌肉组织中的代谢过程均符合一室模型,相应的动力学方程分别为：C血液=17.08×（e-0.0287t-e0.0558t）,C肌肉=11.64×（e-0.0190t-e2.1425t）,C肝脏=15.72×（e-0.0064t-e2.5558t）。说明药饵给药后三聚氰胺在中华鳖体内消除较慢。     

甲砜霉素在红笛鲷体内的组织分布和药代动力学研究

研究腹腔注射和口灌给药方式下甲砜霉素在红笛鲷体内的组织分布和药代动力学特征.甲砜霉素单剂量10 mg/（kg· bw）分别腹注和口灌红笛鲷,给药后取血浆、肌肉、肝脏和肾脏,各组织中药物浓度用HPLC-MS/MS测定,所得药时数据用DAS3.0软件分析.结果显示：两种给药方式下红笛鲷血浆药时数据均符合一级吸收二室模型;血药达峰时间（tp）分别为2.39和4.51 h,血药浓度峰值（Cmax）分别为5.80和5.06 μ.g/mL,消除半衰期（t1/2β）分别为7.25和50.09 h.腹注和口灌给药肌肉、肝脏和肾脏的Cmax分别为2.504和2.678 μ g/g、4.612和4.393 μg/g、12.464和7.509 μg/g,tp分别为6.0和4.0h、2.0和4.0h、1.5和4.0h;甲砜霉素在红笛鲷体内消除速度较慢,肌肉、肝脏和肾脏的t1/2β分别为37.168和33.519 h、22.499和33.649 h、19.672和8.673 h.结果表明：腹注给药方式下甲砜霉素在红笛鲷体内的吸收快于口灌给药,在血浆和肝脏中的消除快于口灌给药,在肌肉和肾脏中的消除则慢于口灌给药.     

磺胺二甲嘧啶在黑鲪体内的药物代谢动力学和残留消除研究

在(14±1)℃水温条件下,对黑鲪单次口灌100 mg/kg体重的磺胺二甲嘧啶,进行药物代谢动力学研究。在(20±2)℃水温条件下,按照《中华人民共和国水产行业标准磺胺类药物水产养殖使用规范》推荐剂量对黑鮶连续5天口灌给予磺胺二甲嘧啶,研究其在黑鮶体内的残留消除规律。血浆、肌肉和肝脏样品采用高效液相色谱检测,DAS2.0药物代谢动力学软件对数据进行处理分析。结果表明磺胺二甲嘧啶在黑鲪血浆、肌肉和肝脏中均符合一室模型,肝脏、血液和肌肉中药物达峰时间分别为6 h,8 h和10 h;峰值浓度分别为26.45μg/g、25.57μg/g和31.15μg/g;连续多次给药后,黑鮶血液、肌肉、肝脏中药物浓度分别在给药后12d、14d、15d后小于最大残留限量要求(0.1mg/kg)。     

氟苯尼考在红笛鲷体内的药代动力学研究

为研究氟苯尼考在红笛鲷体内的药代动力学特征,在水温(20±2)℃条件下,氟苯尼考以10 mg/kg单剂量腹注和口灌健康红笛鲷(Lutjanus sanguineus),采用HPLC-MS/MS测定组织中的药物浓度,数据用DAS3.0软件分析。结果显示,两种给药方式下红笛鲷血浆药时数据均符合一级吸收二室模型;腹注给药后血浆、肝脏、肾脏和肌肉的峰浓度(C_(max))分别为10.62μg/m L、8.36、22.57和4.76μg/g,达峰时间(T_(max))分别为1.2、1.0、1.0和6.0 h,消除半衰期(t_(1/2β))分别为29.76、17.84、17.23和19.48 h;口灌给药后血浆、肝脏、肾脏和肌肉的C_(max)分别为2.35μg/m L、1.45μg/g、4.06μg/g和1.73μg/g,T_(max)分别为2.69、1.5、1.5和4.0 h,t_(1/2β)分别为40.59、12.29、37.78和47.34 h。结果表明,腹注给药方式下氟苯尼考在红笛鲷体内的吸收快于口灌给药,在血浆和肝脏中的消除快于口灌给药,在肌肉和肾脏中的消除则慢于口灌给药。研究结果为氟苯尼考在临床上的合理应用提供了科学依据。     

水产品中喹乙醇及其主要代谢物残留的研究进展

喹乙醇曾作为水产养殖动物饲料添加剂被广泛应用。随着人们对其毒性和危害的认识,对其使用也做出了新的规定。本文对喹乙醇的毒性及其与主要代谢物3-甲基-喹噁啉-2-羧酸(MQCA)的药代动力学、残留检测方法等做一简述。     

A physiologically based pharmacokinetic model for the prediction of the depletion of methyl‐3‐quinoxaline‐2‐carboxylic acid,the marker residue of olaquindox,in the edible tissues of pigs

To estimate the consumer exposure to olaquindox (OLA) residues in porcine edible tissues, a physiologically based pharmacokinetic (PBPK) model for methyl‐3‐quinoxaline‐2‐carboxylic acid (MQCA), the marker residue of OLA, was developed in pigs based on the assumptions of the flow‐limited distribution, hepatic metabolism, and renal excretion. The model included separate compartments corresponding to blood, muscle, liver, kidney, adipose, and an extra compartment representing the remaining carcass. Physiological parameters were determined from literatures. Plasma protein binding, partition coefficients, and renal clearance for MQCA were determined in in vitro and in vivo studies. The metabolic conversion of OLA to MQCA was assumed as a simple, one‐step process, and an apparent first‐order rate constant (k) was employed to describe this metabolic process. The PBPK model was optimized and validated with plasma and tissue data from literatures and our study. Sensitivity analysis and Monte Carlo simulation were also implemented to estimate the influence of model parameters on the goodness of fit. When compared with the observed data, the PBPK model underestimated the MQCA level in all compartments at the early time points, whereas gave excellent predictions of MQCA concentration in porcine edible tissues at later time points. The correlation coefficients between the predicted and observed values were over 0.88. The consistency between the model predictions and the real residues of OLA in pigs proved the good applicability of our model in food safety risk assessment.     

壳聚糖对饲料镉致罗非鱼急性毒性的影响

通过两个试验研究了壳聚糖对饲料中镉致罗非鱼急性毒性的影响。试验1将360尾罗非鱼随机分为两个处理(对照组和试验组),每个处理3个重复,比较壳聚糖添加后饲料镉致罗非鱼96 h半致死剂量的变化情况。对照组一次性投喂镉水平分别为0.00%、0.10%、0.25%、0.50%、1.00%和2.00%的6种对照饲料;试验组饲料镉含量与对照组相同,并加入10%壳聚糖,同法进行饲料镉对罗非鱼的急性毒性试验。试验2将160尾罗非鱼随机分为两个处理,每个处理4个重复,分别投喂镉含量为0.50%的对照组和试验组饲料,研究饲料中添加壳聚糖对镉致罗非鱼半致死时间的影响。试验结果为:两个试验中试验组鱼的死亡率均低于对照组;对照组96 h半致死剂量(LD50)和半致死时间(LT50)分别为(49.67±6.11)mg/kg.BW和(47.76±3.03)h,试验组96 h LD50和LT50分别为(86.05±6.11)mg/kg.BW和(65.20±6.09)h,试验组96 h LD50和LT50与对照组相比差异极显著(P<0.01),表明壳聚糖能够缓解饲料中镉对罗非鱼的急性毒性。     

Comparative plasma and tissue pharmacokinetics and drug residue profiles of different chemotherapeutants in fowls and rabbits

Blood and tissue pharmacokinetics and drug residue profiles of six chemotherapeutants were studied. Ceftriaxone (CEF), intravenously at 50 mg/kg, sulfamonomethoxine (SMM) and sulfaquinoxaline (SQ), orally at 200 mg/kg, and olaquindox (OLA), orally at 50 mg/kg, were administered to young broilers. Penicillin (PEN), intramuscularly at 200 000 U/kg, and albendazole (ALB), orally at 20 mg/kg, were given to rabbits. For each drug, 13–18 groups ( n = 5–10 individuals/group) of the dosed animals were killed at different post-dosing times. Drug and/or metabolite concentrations in plasma, liver, kidney, heart, lung, and muscle tissues were analysed by HPLC procedures. Multi-exponential kinetic models were fitted to the observed tissue concentration-time data by applying a non-linear least-squares regression computer program. Tissue half-life, peak tissue concentration, and time of peak tissue concentration were determined. Half-life of CEF, SMM, SQ, OLA, PEN, ALB, and two metabolites of ALB (sulfoxide and sulfone) in various tissues ranged 0.6–1.4, 4.7–9.0, 4.5–18.9, 1.8–3.1, 0.9–3.0, 3.4–9.6, 5.0–16.1 and 7.4–12.2 h. The times required for CEF, SMM, SQ, OLA, PEN, and ALB residue concentrations to decline to 0.1 μg/g in various tissues ranged from 5.0–11.6. 70.0–110.5. 114.0–179.8, 21.3–30.3,4.1–24.8 and 47.8–84.4 h. Drug kinetic characteristics in tissues differed significantly from those in plasma, and also varied from tissue to tissue. It is necessary, therefore, to evaluate tissue kinetics when designing dosage regimens in tissue infection chemotherapy with these drugs. Knowledge of tissue kinetics is also important in predicting and controlling drug residues in edible tissues of food-producing animals.     

喹乙醇对鲤鱼的毒理学研究进展

喹乙醇是饲料中常见的促生长剂,适量使用有利于鱼类的生长,但过量喹乙醇会对鲤鱼鳃、肾脏、肝脏等组织产生一系列的毒害作用。因此在水产养殖中应该对喹乙醇的使用量加以控制。本文从组织受损、营养代谢和生理生化功能等方面综述了喹乙醇对鲤鱼的毒性及作用机理。     

Metabolism and residue depletion of albendazole and its metabolites in rainbow trout, tilapia and Atlantic salmon after oral administration

Metabolic and residue depletion profiles of albendazole (ABZ) and its major metabolites in three fish species, rainbow trout, tilapia and Atlantic salmon are reported. Based on these profiles, similarities (or dissimilarities) between species will determine the potential to group fish species. ABZ at 10 mg/kg body weight was incorporated into fish food formulated in a gelatin base or in gel capsule and fed as a single dose to six fish from each species. Rainbow trout were held three each in a partitioned 600-L tank. Tilapia and Atlantic salmon were housed in separate 20-L tanks. Samples of muscle with adhering skin were collected at 8, 12, 18, 24, 48, 72, and 96 h postdose from trout kept at 12 degrees C, at 4, 8, 12, 24, 48, 72, 96, 120, and 144 h postdose from tilapia kept at 25 degrees C and at 8, 14, 24, 48, 72, and 96 h postdose from Atlantic salmon kept at 15 degrees C. The samples were homogenized in dry ice and subjected to extraction and cleanup procedures. The final extracts were analyzed for parent drug ABZ and its major metabolites, albendazole sulfoxide (ABZ-SO), albendazole sulfone (ABZ-SO2) and albendazole aminosulfone using high-performance liquid chromatography with fluorescence detection. ABZ was depleted by 24 h in trout and tilapia and by 48 h in salmon; ABZ-SO, a pharmacologically active metabolite, was depleted by 48 h in tilapia, by 72 h in rainbow trout and was present until 96 h in salmon; and low levels of ABZ-SO2 and albendazole aminosulfone, both inactive metabolites, were detectable at least till 96 h in all three fish species.     

Hematology and plasma chemistry reference intervals for cultured tilapia (Oreochromis hybrid)

Abstract: Tilapia are a commonly aquacultured fish yet little is known about their normal physiology and response to disease. In this study we determined the results of complete hematologic (n = 40) and plasma biochemical profiles (n = 63) in production tilapia ( Oreochromis hybrids). The fish were raised in recirculating systems with a high stocking density (120 g/L), and were in the middle of a 15-month production cycle. Blood was analyzed using standard techniques, and reference intervals were determined using nonparametric methods. Non-production tilapia (n = 15) from low-density tanks (4 g/L) also were sampled; the clinical chemistry results were compared to reference intervals from the fish raised in high-density tanks. Differences were noted in plasma protein, calcium and phosphorus concentrations, such that reference intervals for high-density production tilapia were not applicable to fish raised under different environmental and management conditions.     

The Plasma Kinetics and Tissue Distribution of Enrofloxacin and its Metabolite Ciprofloxacin in the Muscovy Duck

Intorre, L., Mengozzi, G., Bertini, S., Bagliacca, M., Luchetti, E. and Soldani, G., 1997. The plasma kinetics and tissue distribution of enrofloxacin and its metabolite ciprofloxacin in the Muscovy duck. Veterinary Research Communications, 21 (2), 127-136The disposition and tissue distribution of enrofloxacin and of its main metabolite ciprofloxacin were investigated in ducks after oral or intramuscular administration of a single dose of 10 mg/kg enrofloxacin. Plasma and tissue concentrations were determined by a HPLC method. The peak concentrations of enrofloxacin after intramuscular administration (1.67 µg/ml at 0.9 h) were higher than after an oral dose (0.99 µg/ml at 1.38 h). The relative bioavailability of enrofloxacin after administration directly into the crop was 68%, while the metabolic conversion of enrofloxacin to ciprofloxacin was quite low (<10%) with both routes of administration. High tissue concentrations and high tissue:plasma concentration ratios were demonstrated for enrofloxacin and ciprofloxacin 24 h after treatment. It was concluded that a dose of 10 mg/kg per day provides serum and tissue concentrations sufficiently high to be effective in the control of many infectious diseases of ducks.     

Role of Endogenous Opioids in Modulating Some Immune Functions in Hybrid Tilapia

Abstract

Social confrontation between two hybrid tilapias (Mozambique tilapia Tilapia mossambica × wami tilapia Tilapia urolepis) results in establishment of a victorious (dominant) and a defeated (subordinate) fish. Two measures of cell-mediated immune responses were made in representative groups of victors and losers. Aggressive encounters were followed by a marked suppression of nonspecific cytotoxicity and mitogen-stimulated proliferation of head kidney leukocytes of losers. Immunosuppression appeared to be mediated by one or more humoral factors released into the serum of defeated fish. These factors were partially blocked by intramuscular administration of the opioid antagonist naltrexone (1.0 mg/100 g body weight) 1 h prior to social confrontation. This antagonism suggests that endogenous opioids are involved in immunosuppression and immunomodulation in hybrid tilapias.