盐酸多西环素注射液在猪体内残留消除规律研究

为研究自制盐酸多西环素注射液在猪体内的残留消除规律,以10 mg/kg剂量给健康猪肌内注射盐酸多西环素注射液,每日1次给药,连续三次。在最后一次给药后7、14、21、28和35 d时间点采集肌肉、肝脏、肾脏、脂肪和注射部位肌肉,用UPLC-MS/MS法测定组织中多西环素残留量。结果表明,给药35 d后,肌肉、肝脏、肾脏、脂肪和注射部位肌肉中的多西环素残留量分别为18、24、69、10、59μg/kg,均低于最高残留限量。用WT1.4软件计算休药期,盐酸多西环素注射液在猪肌肉、肝脏、肾脏、脂肪和注射部位肌肉中的休药期分别为33.9、23.8、24.8、0和36.9 d,为保证兽药安全使用、消费者身体健康与食品安全,建议盐酸多西环素注射液在猪的休药期为42 d。     

恩诺沙星可溶性粉在北京油鸡体内残留消除规律研究

为研究恩诺沙星可溶性粉在北京油鸡体内的残留消除规律，以确定休药期，试验采用推荐剂量（75 mg/L）和2倍推荐剂量（150 mg/L）恩诺沙星自由饮水方式连续对北京油鸡给药5 d，在最后一次给药后0（停药后4 h）、1、3、5、7、9、12和15 d，采集北京油鸡肝脏、肾脏、肌肉和脂肪，采用高效液相色谱串联质谱法测定各组织中的恩诺沙星及其代谢物环丙沙星的残留量，并用WT1.4软件计算休药期。结果显示，推荐剂量5%恩诺沙星可溶性粉在北京油鸡各组织的休药期分别为肝脏7.1 d、肌肉3.8 d、肾脏5.2 d、脂肪4.4 d,2倍推荐剂量的休药期分别为肝脏9.6 d、肌肉4.2 d、肾脏6.4 d和脂肪8.4 d。结果表明，恩诺沙星在北京油鸡的休药期可设置为8 d。     

长效盐酸多西环素注射液在猪体内残留的消除规律

在常规饲养条件下,对35头健康成年猪按10 mg/kg体质量的剂量肌肉注射10%长效盐酸多西环素注射液,给药2次,给药间隔时间为48 h。第2次给药后12 h及2、5、9、14、192、5 d分别屠宰5头猪,分别采取每头猪的肌肉、肝脏、肾脏、皮肤+脂肪和注射位点肌肉等5种组织,用高效液相色谱法进行残留量测定。结果表明:在第2次给药后19 d,多西环素在各组织均能检测到,且残留均低于残留限量。多西环素残留浓度大小顺序:注射部位(肾脏(肝脏(皮脂(肌肉。采用WT1.4软件制定的统计方法来处理猪组织中药物浓度-时间数据,以制定休药期。     

恩诺沙星在猪组织中残留消除规律研究

在常规饲养条件下,对健康猪按2.5 mg/kg体重的剂量肌肉注射2.5%恩诺沙星注射液,每日2次,连续注射3 d.停药后第2、4、6、8、10、12、14天分别屠宰4头猪.分别采取每头猪的肌肉(注射部位)、脂肪(腹脂)、肝和肾脏等4种组织,用高效液相色谱法进行残留量测定.结果表明:残留在肌肉、脂肪组织中的药物消除较快,第8天总残留量(恩诺沙星 环丙沙星)已下降至检测限(20μg/kg)以下;肝和肾脏组织中的药物消除缓慢,第14天测得猪肾中药物总残留量为40μg/kg.     

恩诺沙星可溶性粉在白羽乌骨鸡组织中残留消除规律研究

为研究恩诺沙星可溶性粉在乌骨鸡体内的残留消除规律。50只11日龄健康白羽乌骨鸡,随机分为2组,给药组40只,对照组10只,给药组混饮恩诺沙星水溶液,浓度为75 mg/L,2次/d,连续用药5 d,对照组不给任何抗菌药物,与给药组同环境饲养。在最后一次给药后9、20、40、70、106 d采集肌肉、肝脏、肾脏、皮脂等样本,经LC-MS/MS法测定组织中的恩诺沙星及环丙沙星残留量,并利用WT1.4软件计算休药期。恩诺沙星可溶性粉在乌骨鸡肌肉、肝脏、肾脏及皮脂中的休药期分别是102.48、0、41.93、116.38 d。为保证消费者健康和食品安全,推荐恩诺沙星可溶性粉在乌骨鸡体内的休药期应大于117 d。     

土拉霉素在猪体内残留消除规律的研究

本研究旨在分析土拉霉素在猪体内的残留消除规律并为制定休药期提供依据。采用猪颈部一次性肌内注射土拉霉素注射液,注射剂量为2.5mg.kg-1体质量,分别在给药后第0.5,5,12,18,25,36,48天,各宰杀5头取样。样品经乙腈提取,正己烷脱脂,C18固相萃取柱(SPE)净化后用高效液相色谱—串联质谱仪分析。结果显示,给药后第0.5天注射部位药物浓度最高,第36天所有组织的药物浓度均低于最高残留限量(MRL)。用WinNonlin软件分析各组织中的消除动力学参数,消除快慢依次为注射部位,肝脏,皮脂,肌肉,肺脏和肾脏,其消除半衰期(t1/2β)分别为117.06,193.14,197.60,207.64,228.99和232.61h。肺脏的药时曲线下面积(AUC)为1 220.59μg.h.g-1仅次于注射部位及肾脏,显著高于肌肉,肝脏及皮脂。由于肾脏为代谢器官,因此可确定肺脏为土拉霉素作用的靶部位。根据欧美等国家对土拉霉素制定的最高残留限量,计算得注射部位的休药期最长,为33d。结果提示土拉霉素注射液吸收迅速,体内分布广,作用时间长。建议休药期为33d。     

喹烯酮在猪组织中的残留研究

目的 :建立起定量测定猪肝脏、肾脏、肌肉、脂肪食用组织中喹烯酮的高效液相色谱检测方法 ,依据测定的结果制定最高残留限量 ,定出其休药期。方法 :猪 45头 ,公母各半 ,按正常饲料添加喹烯酮 50 mg/ kg饲喂 2 .5月后 ,分别于4h、1 d、2 d、3 d、4d、6d、8d、1 2 d、1 5d采样。检测采用 Prodigy5μ Phenyl-3色谱分析柱 (4.6mm× 2 50 mm5μm icron) ,Waters TM486可变波长紫外检测器 ,甲醇 -水 (70∶ 3 0 )为流动相。组织样品用乙酸乙酯、乙腈、正已烷、氯仿等试剂提取处理纯化后进样 ,在 3 1 2 nm波长处检测 ,流速为 1 .0 m L·min- 1。结果 :标准曲线的线性范围为 :脂肪、肝脏 ,0 .0 0 5～ 0 .80 0μg· g- 1;肾脏、肌肉 ,0 .0 0 8～ 0 .0 80μg· g- 1。它们的复相关系数均大于 0 .99。精密度考察喹烯酮的日内各组织各浓度的 RSD(相对标准差 )均小于1 2 % ,日间测得各组织各浓度的 RSD均小于1 8.5%。喹烯酮在肌肉、脂肪、肾脏中均无残留 ,而在肝脏中的残留量也很小 ,4d以后再无残留。结论 :本试验测定方法灵敏度高 ,重复性好。停药后 4h所有可食用猪组织中喹烯酮浓度均低于计算所得的安全组织浓度 ,故该药在猪使用上无休药期 ,即休药期为零天。     

恩诺沙星混悬液的研制及其在鸡组织中的残留研究

以恩诺沙星为主药,采用正交试验筛选配方,研制恩诺沙星混悬液,并对该制剂的药剂学特征及其在鸡组织中的残留进行研究。药剂学研究表明,混悬液的性状、pH及药物含量均符合混悬剂质量要求,且稳定性良好、易于再分散。健康鸡在饮水中添加75 mg/L(以恩诺沙星计)混悬液,自由饮水,连续用药5 d后休药;休药第5天,肌肉、肝脏及"皮肤+脂肪"组织中药物总残留量(恩诺沙星+环丙沙星)分别为11.12±10.53、79.29±28.86、50.08μg/kg±22.09μg/kg,而肾脏组织未检出;休药第8天,肌肉、肾脏、肝脏组织中均未检出恩诺沙星及环丙沙星,"皮肤+脂肪"的总残留量为13.84μg/kg±10.82μg/kg。采用WT1.4软件处理数据,计算出该混悬液在鸡体内的休药期为6 d。     

恩诺沙星固体分散剂在肉鸡组织中残留的研究

为了研究恩诺沙星固体分散剂在肉鸡组织中的残留情况,试验选择150只1日龄AA肉鸡,试验组喂养至35日龄在饮水中添加75 mg/L恩诺沙星固体分散剂,自由饮水,连续用5 d后休药,采集不同时间的样本用高效液相色谱法(HPLC)进行检测。结果表明:休药第5天,肝脏、胸肌及脂肪组织中药物总残留量(恩诺沙星+环丙沙星)分别为(77.07±15.21),(12.56±9.65),(26.36±11.72)μg/kg,而肾脏组织中未检出;休药第7天,肝脏、肾脏、胸肌及脂肪组织中均未检出恩诺沙星及环丙沙星。采用WT 1.4软件处理试验数据,肝脏、肾脏、胸肌和脂肪的休药期(WDT)分别为5.92,4.36,5.21,5.63 d。说明肉鸡按照推荐剂量饮水给药,建议休药期至少为6 d。     

恩诺沙星及其代谢物在方正银鲫组织中的代谢及消除规律

近年来水产养殖中的常用药物恩诺沙星在鲫中的残留问题比较突出,但目前国家未对其在鲫中的休药期作出明确规定。为做到鲫养殖中科学合理使用恩诺沙星,在12~15℃水温条件下,以60mg/kg.b.w.剂量,对体质量为(250±10)g的健康方正银鲫(Carassius auratus gibelio)灌服恩诺沙星;在灌服后0~120d内不间断采样,用高效液相色谱-串联质谱仪检测,研究恩诺沙星及其代谢产物环丙沙星在方正银鲫鳃、血浆、肌肉、皮肤、肝脏和肾脏中的代谢及消除规律,从而为恩诺沙星在方正银鲫中的休药期制定提供参考。结果显示:灌药后,恩诺沙星在方正银鲫血浆、肌肉、肝脏、鳃、肾脏和皮肤中的达峰时间tmax分别为9、18、24、24、48和48h,肾脏、肝脏、肌肉、血浆、鳃和皮肤中的达峰浓度cmax分别为30.490、21.372、18.715、16.636、15.157和11.663mg/kg;皮肤中的消除半衰期t1/2β最大,为338.2h,血浆中最小,为93.303h;代谢产物环丙沙星的代谢及消除趋势与恩诺沙星大致相同,血浆中达峰值产生最早,tmax为18h,肾脏中的峰浓度最大,cmax为547.26μg/kg。结果表明,方正银鲫以单次口灌60mg/kg.b.w.剂量恩诺沙星,皮肤和肌肉中的恩诺沙星和环丙沙星总量需要1200度日才能满足限量要求。本研究为恩诺沙星在鲫鱼养殖中的科学使用提供了数据支撑。     

三种喹诺酮类药物在鸡蛋中残留消除规律的研究

建立了一种检测三种喹诺酮类药物在鸡蛋中残留的高效液相色谱-荧光检测法。利用建立的方法对三种喹诺酮类药物在产蛋期蛋鸡用药后鸡蛋中的浓度进行了测定,并根据测定值研究了鸡蛋中药物的残留消除规律。400kg水中分别添加不同含量的诺氟沙星、氧氟沙星、恩诺沙星．连续给药3d,使用高效液相色谱法对鸡蛋中三种喹诺酮类药物残留进行分析。结果表明,停药8d时,鸡蛋中检出的诺氟沙星和氧氟沙星的浓度均低于10μg/kg;停药12d时,鸡蛋中检出的恩诺沙星的浓度低于10μg／蚝。建议诺氟沙星和氧氟沙星在临床上蛋鸡产蛋前10d左右停用,恩诺沙星在临床上蛋鸡产蛋前14d左右停用。     

Pharmacokinetic variables and tissue residues of enrofloxacin and ciprofloxacin in healthy pigs

OBJECTIVES: To determine pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin after a single i.v. and i.m. administration of enrofloxacin and tissue residues after serial daily i.m. administration of enrofloxacin in pigs. ANIMALS: 20 healthy male pigs. PROCEDURE: 8 pigs were used in a crossover design to investigate pharmacokinetics of enrofloxacin after a single i.v. and i.m. administration (2.5 mg/kg of body weight). Twelve pigs were used to study tissue residues; they were given daily doses of enrofloxacin (2.5 mg/kg, i.m. for 3 days). Plasma and tissue concentrations of enrofloxacin and ciprofloxacin were determined. Residues of enrofloxacin and ciprofloxacin were measured in fat, kidney, liver, and muscle. RESULTS: Mean (+/-SD) elimination half-life and mean residence time of enrofloxacin in plasma were 9.64+/-1.49 and 12.77+/-2.15 hours, respectively, after i.v. administration and 12.06+/-0.68 and 17.15+/-1.04 hours, respectively, after i.m. administration. Half-life at alpha phase of enrofloxacin was 0.23+/-0.05 and 1.94+/-0.70 hours for i.v. and i.m. administration, respectively. Maximal plasma concentration was 1.17 +/-0.23 microg/ml, and interval from injection until maximum concentration was 1.81+/-0.23 hours. Renal and hepatic concentrations of enrofloxacin (0.012 to 0.017 microg/g) persisted for 10 days; however, at that time, ciprofloxacin residues were not detected in other tissues. CONCLUSIONS AND CLINICAL RELEVANCE: Enrofloxacin administered i.m. at a dosage of 2.5 mg/kg for 3 successive days, with a withdrawal time of 10 days, resulted in a sum of concentrations of enrofloxacin and ciprofloxacin that were less than the European Union maximal residue limit of 30 ng/g in edible tissues.     

恩诺沙星混悬液在猪体内残留消除规律研究

采用高效液相色谱法研究恩诺沙星(口服)混悬液在猪体内各组织中的残留消除规律.恩诺沙星(口服)混悬液,按每头猪10 mg/kg体重的剂量灌服给药,连续使用3 d之后,宰杀猪,取组织.组织样品经磷酸盐缓冲液提取,C18固相萃取柱净化,过膜,用流动相0.05 mol/L磷酸溶液/三乙胺一乙腈(82+18)溶解,微孔过滤,进行...     

Intramuscular and oral disposition of enrofloxacin in African grey parrots following single and multiple doses

The intramuscular (IM) and oral (PO) disposition of enrofloxacin, a new fluoroquinolone antimicrobial drug, were evaluated in African grey parrots. Peak enrofloxacin concentration, mean (+/- SEM), at 1 h following a 15-mg/kg IM dose was 3.87 (+/- 0.27) micrograms/ml and declined with a mean residence time of 3.05 h. Peak enrofloxacin plasma concentrations at 2 to 4 h following oral doses of 3, 15, and 30 mg/kg were 0.31 (+/- 0.11), 1.12 (+/- 0.11), and 1.69 (+/- 0.23) micrograms/ml, respectively, and declined with a mean residence time of 3.44-5.28 h. The relative bioavailability of the 15-mg/kg oral dose was 48%. An equipotent metabolite, ciprofloxacin, was detected in plasma at concentrations ranging from 3 to 78% of those of enrofloxacin. Enrofloxacin concentrations and area under the curve were significantly lower, the mean residence time significantly shorter and the ciprofloxacin/enrofloxacin ratios higher, following 10 days of oral treatment at 30 mg/kg every 12 h. Following 10 days of treatment, no significant biochemical changes were noted; however, polydipsia and polyuria occurred in treated birds, but resolved quickly upon discontinuation of enrofloxacin administration. These studies indicate that a rational starting dose for enrofloxacin in psittacines (7.5-30 mg/kg BID) should be higher than those in other domestic animals.     

Accumulation and elimination of enrofloxacin and its metabolite ciprofloxacin in the ridgetail white prawn Exopalaemon carinicauda following medicated feed and bath administration

Accumulation and elimination of enrofloxacin and its metabolite ciprofloxacin were evaluated in Exopalaemon carinicauda following medicated feed at dose of 10 mg/kg weight body per day for five consecutive days and 10 mg/L bath for five consecutive days at 18 °C. At different times, nine ridgetail white prawns were randomly selected from the tank and sampled after the last medicated feed or bath administration. The concentration of enrofloxacin and ciprofloxacin in the main tissues (hepatopancreas, muscle, gill, and ovary) was detected by HPLC. The results showed that the maximum concentrations of enrofloxacin were 3.408 ± 0.245, 0.554 ± 0.088, 0.789 ± 0.074, and 0.714 ± 0.123 μg/g for hepatopancreas, muscle, gill, and ovary, respectively, at 1 day after the last medicated feed treatment. The enrofloxacin concentrations were 2.389 ± 0.484, 0.656 ± 0.012, 0.951 ± 0.144, and 3.107 ± 0.721 μg/g in hepatopancreas, muscle, gill, and ovary, respectively, at 1 day after the last bath administration. Ciprofloxacin could be detected in hepatopancreas, muscle, gill, and ovary. However, the concentrations of ciprofloxacin were much lower in comparison with that of enrofloxacin in various tissues. The concentrations of enrofloxacin plus ciprofloxacin in hepatopancreas, muscle, gill, and ovary followed an eliminating pattern during the sampling time after the two routes of administration. Based on data derived from this study, to avoid the enrofloxacin and ciprofloxacin residue in E. carinicauda, it should take at least 20 and 25 days to wash out the drug from the tissues after the last medicated feed and bath administration with enrofloxacin, respectively. These results helped the Chinese fishery department to lay down the current guidelines on enrofloxacin plus ciprofloxacin withdrawal periods for farmed shrimp.     

Concentration of enrofloxacin and its metabolite ciprofloxacin in canine matrices of the locomotor system

Due to its pharmacodynamic and pharmacokinetic properties, the use of enrofloxacin may be indicated in canine osteomyelitis, but there is insufficient data on its distribution within the musculoskeletal tissues. The dogs used in this study were 31 regular veterinary orthopaedic patients. Four hours after their oral or subcutaneous treatment with 10 mg/kg enrofloxacin (Baytril; Bayer, Leverkusen, Germany) once daily for 1 or 3 days, the concentration of enrofloxacin and its main metabolite ciprofloxacin was quantified in plasma, bone, musculature and other matrices of the locomotor system by high pressure liquid chromatography with fluorescence-detection after homogenization and solid phase extraction of the samples. By oral or subcutaneous administration of enrofloxacin once daily for 3 days, higher concentrations of the active constituents in the samples were achieved than by single treatment. Nevertheless, even after single injection, minimal inhibitory enrofloxacin concentrations of up to 0.5 microg ml or microg/g sample against most pathogens of osteomyelitis were exceeded. In the musculature, on average, higher concentrations of active constituents were detected than in less perfused matrices (bones and synovial membranes) at sampling time. The enrofloxacin diffusion into inflamed bone was higher compared with mechanically damaged bone, whereas for ciprofloxacin it was lower. In conclusion, a dosage of 10 mg/kg enrofloxacin is sufficient to exceed the minimal inhibitory concentrations in osteomyelitic bone against most pathogens that are sensitive in vitro, but clinical efficacy remains to be evaluated.     

纳米金-核酸适配体可视化检测蜂蜜中恩诺沙星的方法研究

目的 建立纳米金-核酸适配体可视化检测畜产品中恩诺沙星的方法。方法 首先利用还原法合成纳米金（gold nanoparticles, AuNPs）颗粒,利用紫外分光光度计对实验原理进行验证,优化了实验条件,建立了恩诺沙星浓度和特定波长下吸光度值之间的关系式。同时也验证了该方法的特异性。结果 所得线性回归方程在低浓度时为y=0.6377x+0.89495,R2=0.99026,方法检出限为0.018 CFU/mL;所得线性回归方程在高浓度时为y=0.04288x+0.95578,R2=0.99812,方法检出限为0.265 CFU/mL。方法除可用来检测恩诺沙星外,还可用于检测盐酸恩诺沙星,具有一定的特异性。对恩诺沙星实际样品测定的回收率为95.5%~97.8%,相对标准偏差小于10%。结论 方法操作方便简便,成本低,检测时间短,可用于畜产品中恩诺沙星快速定量检测。     

Tissue distribution and disposition kinetics of enrofloxacin in healthy and E. coli infected broilers

Concentrations of enrofloxacin equivalent activity were determined by microbiological assay in the plasma of healthy and E. coli-infected broilers following single intravenous and oral administrations at 10 mg/kg. Tissue distribution and residue-depletion following multiple oral doses (10 mg/kg for 3 successive days) were investigated. Pharmacokinetic variables were determined using compartmental and non-compartmental analytical methods. Plasma enrofloxacin concentrations after intravenous dosing to healthy and infected birds were best described by a two-compartments model. Enrofloxacin concentrations in plasma of infected birds were lower than those of healthy ones. The disposition kinetics of intravenously administered drug in healthy and infected birds were somewhat different. The elimination half-life (t1/2 beta) was 4.75 vs. 3.63 h; mean residence time (MRT) was 6.72 vs 4.90 h; apparent volume of the central compartment (Vc) was 1.11 vs 1.57 l/kg; rate constant for transfer from peripheral to central compartment (k21) was 1.15 vs 1.41 h-1 and total body clearance (ClB) was 0.35 vs 0.53 l/h/kg in healthy and infected birds, respectively. After oral administration, the absorption half-life (t1/2abs) in the infected birds was significantly longer than in healthy birds, while elimination half-life (t1/2el) and MRT were significantly shorter. Bioavailability was higher in infected birds (72.50%) as compared to healthy ones (69.78%). Enrofloxacin was detected in the tissues of healthy and infected birds after daily oral dosing of 10 mg/kg for 3 days. It was more concentrated in liver, kidney, and breast muscle. The minimal inhibitory concentration (MIC) of enrofloxacin against E. coli was 0.064 microgram/ml. On the basis of maintaining enrofloxacin plasma concentrations over the MIC, a dose of 10 mg/kg given intravenously every 20.14 hrs or orally every 20.86 hrs should provide tissue concentrations effective against E. coli infection in chickens.     

三种恩诺沙星注射液在猪体内的药物代谢动力学研究

三组猪分别按2.5 mg/kg的剂量肌肉注射拜有利5%、恩诺沙星注射液A、恩诺沙星注射液B三种药物,HPLC法测定血药浓度,Winnonlin6.1软件拟合血药浓度—时间数据,计算参数。三种注射液均符合一室开放模型,峰浓度分别为:0.87、0.63、0.49μg/mL,AUC分别为6.32、5.31、3.45 h.μg.mL-1。实验结果表明,拜有利5%在猪体内的药代动力学参数优于注射液B,注射液B的优于注射液A,提示恩诺沙星注射液B与拜有利5%相比临床防治效果略差,药物吸收可做进一步改进。