长效土霉素注射液在猪体内的生物等效性研究

研究自制长效土霉素注射液与进口长效土霉素注射液(得米先注射液)在猪体内单剂量注射的药代动力学和生物等效性,为临床应用提供参考和依据.采用双处理、双周期随即交叉试验设计.12头健康猪分为两组,分别先后单剂量肌肉注射自制长效土霉素注射液与得米先注射液,用高效液相色谱法测定血浆中土霉素的浓度,3P97软件计算药代动力学参数.自制长效土霉素注射液与参比制剂的主要药动学参数如下:AUC分别为(145.41 ±3.59)、(159.28 ±4.47) μg·mL-1·h,T1/2β分别为(84.776±2.21)、(72.740±1.95)h,Cmax分别为(3.519±1.66)、(3.924±1.34)μg/mL,Tmax分别为(1.848±0.54)、(1.760±0.41)h.采用3P97药代动力学软件分析比较AUC和Cmx90％置信区间,自制长效土霉素注射液的AUC、Cmax的90％置信区间分别为94.7％～105.2％、85.0％ ～114.6％,分别落在参比制剂的80％～125％、70％ ～143％范围内,两组参数差异不显著(P＞0.05),结果表明二者具有生物等效性.     

影响长效土霉素注射液稳定性的几个因素

本试验适当改变长效土霉素注射液的处方和溶解条件,加入适当稳定剂,调整常规的生产工艺.结果表明,改进后的长效土霉素注射液的稳定性大大提高,颜色在标准范围之内,经105℃流通蒸气灭菌60 min,未见颜色变化,经微生物效价测定,含量为100.5%,可信限6.3%.说明采用该生产工艺能提高长效土霉素注射液的稳定性.     

紫外分光光度法测定长效土霉素注射液含量方法的建立

以0.01 mol/L盐酸溶液为参比液,采用紫外分光光度法在268 nm波长处测定长效土霉素注射液中土霉素的含量.结果表明,土霉素在5 μg/mL～30 μg/mL浓度范围内,其吸光度与浓度呈良好的线性关系,相关系数r=0.999 9,平均回收率为99.34%,变异系数为0.46%(n=6).该方法操作简便、快速、结果准确,适于作为生产企业中间产品的质量控制方法.     

2种头孢氨苄片在比格犬体内的药代动力学及生物等效性试验

【目的】研究头孢氨苄片受试制剂和参比制剂在比格犬体内的生物等效性。【方法】采用双周期和双序列交叉设计,将22只健康比格犬随机分成2组,按30 mg/kg BW分别单剂量口服头孢氨苄片受试制剂Trolevis~?300和参比制剂Rilexine~?300,于给药前(0 h)和给药后0.5、1、1.5、2、2.5、3、4、6、8、12、17和24 h从臂头静脉采血。对超高效液相色谱串联质谱(UPLC-MS/MS)方法进行特异性、线性、检测限、准确度、精密度、稳定性等方法学考察。利用建立好的UPLC-MS/MS方法测定血浆中的药物浓度,并用WinNonlin^TM 8.1软件对药代动力学参数进行分析计算。【结果】方法学结果显示,在100～5 000 ng/mL浓度范围内相关性良好,相关系数(R²)≥0.99,标准曲线方程为y=10.6828x-176.481;高、中、低3个浓度的相对回收率平均值分别为105.63%、104.35%和102.40%;日内和日间变异系数均<15%;检测限为50 ng/mL,定量限为100 ng/mL。药代动力学结果...     

长效土霉素注射液在猪体内的药动学及相对生物利用度研究

对7头健康猪随机交叉设计进行单剂量肌肉注射国产30％长效土霉素注射液和进口20％长效土霉素注射液药动学试验,给药剂量以土霉素计均为20mg／kg体重。用高效液相色谱法测定血药浓度,血药浓度一时间数据用MCPKP计算机程序处理。30％长效土霉素注射液和20％长效土霉素注射液主要药动学参数分别为：吸收半衰期（t1／2ka）为（0．088±0．016）、（0．140±0．076）h;消除半衰期（t1／2β）为（52．499±22．885）、（36．481±21．673）h;达峰时间（Lmax）为（0．609±0．100）、（0．832±0．373）h;峰浓度（Cmax）为（4．956±1．171）、（5．0184-0．948）μg／mL;药时曲线下面积（AUG）为（112．483±18．135）、（109．877±19．949）mg／L·h;以20％长效土霉素注射液为对照物,30％长效土霉素注射液的相对生物利用度（F）为（105．368±26．027）％。结果表明,国产30％长效土霉素注射液与进口20％长效土霉素注射液相比,主要药动学参数无显著差异。此结论为临床合理使用该剂型提供了依据和指导。     

The Pharmacokinetics of a Long-acting Oxytetracycline Formulation in Healthy Dogs and in Dogs Infected with Ehrlichia canis

The pharmacokinetic properties of oxytetracycline were studied following a single injection of a long-acting formulation (20 mg/kg body weight) into the semimembranosus muscle of healthy dogs and of dogs that had been experimentally infected with Ehrlichia canis. The disposition curves of the long-acting oxytetracycline formulation before and after infection were best described by a bi-exponential decline after a first-order absorption. The mean maximum serum concentration (C _max) following infection was significantly lower and the time taken to attain this concentration (t _max) was significantly shorter than that in the healthy dogs. The mean apparent elimination half-life (t _1/2) was significantly increased following infection. The corresponding rate constant () was significantly decreased. The absorption half-life (t _1/2ab) was significantly decreased after infection. The volume of distribution at steady state (V _dss) increased significantly following infection. It was concluded that the pharmacokinetic behaviour of a long-acting oxytetracycline in dogs after intramuscular administration is characterized by a two-compartment model with a slow elimination phase. This could be due to flip-flop kinetics. The febrile reaction in experimental E. canis infection affected some pharmacokinetic parameters of oxytetracycline.     

长效土霉素注射液在猪体内的药代动力学研究

建立了土霉素在猪血浆中含量测定的高效液相色谱法，研究了其在猪体内的药代动力学。土霉素检测的线性范围为0．25～32．0lμg／mL，相关系数为0．9997，最低定量限为0．25μg／mL。药代动力学研究表明，给猪单剂量肌肉注射土霉素25mg／kg体重后，其血药浓度一时间曲线符合一级吸收二室模型，参数为Tmax=2h,Cmax=7．62lμg／mL,t1/2β=69．315h，V1／F=4．648L／kg，说明长效土霉素在体内逐渐吸收和广泛分布后，在组织中能长时间地维持较高的血药浓度，能达到长效之目的。本试验能对兽药药代动力学研究和制定长效土霉素注射液合理给药方案提供参考。     

澳洲白绵羊和黑杜泊羊与湖羊杂交试验初探

本文利用澳洲白绵羊和黑杜泊羊与湖羊开展杂交试验,对其生长发育和繁殖性能进行观测,筛选适合临夏地区肉羊最佳杂交组合,促进临夏肉羊生产提质增效,加快推进肉羊产业高产、优质、高效健康发展。实验结果表明:产羔率湖羊>黑杜湖F1>澳湖F1,繁殖成活率澳湖F1>黑杜湖F1>湖羊;羔羊初生重三个组合之间差异均不显著(t<0.05),三月龄六月龄重澳湖F1与湖羊、黑杜湖F1与湖羊差异极显著(t>0.01);杂交羔羊出生时体高、体长均不显著(t<0.05),黑杜湖F1与澳湖F1两个杂交组合的胸围与湖羊之间差异极显著(t>0.01);三月龄两个杂交组合管围与湖羊之间差异极显著(t>0.01);六月龄体高黑杜湖F1与湖羊差异不显著(t<0.05),澳湖F1与湖羊差异显著(t>0.05),体长三个组合之间差异均不显著(t>0.05),胸围和管围澳湖F1与黑杜湖F1两个杂交组合与湖羊之间差异均为显著(t>0.05)。     

盐酸土霉素可溶性粉在肉鸡组织中的残留消除研究

在常规养殖环境中,对不同日龄肉鸡分别给予250 mg/L和333 mg/L 50%盐酸土霉素可溶性粉,集中饮水给药,每日1次,连续5 d。停药后4 h,1 d,3 d,5 d,6 d,7 d,8 d,9 d,10 d宰杀肉鸡,采集可食性组织(肌肉、肝脏和鸡胗)样品,肌肉、肝脏和鸡胗组织中的残留量采用UPLC-MS/MS测定。结果表明:土霉素主要残留在肝脏组织中;肌肉、肝脏和鸡胗组织的消除速率相似;停药5 d后,两个剂量组的肌肉、肝脏中土霉素残留量均低于最高残留限量(MRL)。休药期计算软件WTl.4结果显示,上述两种方法给药后,建议休药期分别为7、8 d。     

五种土霉素注射液在猪体内的药物代谢动力学比较研究

对五种土霉素注射液产品(A、B、C、D和得米先20%)进行了猪体内的药代动力学比较研究。五组猪分别按20 mg/kg的剂量耳后肌肉注射,HPLC测定血药浓度,3P97软件拟合血药浓度-时间数据,计算药代动力学参数。五种长效土霉素注射液均符合二室开放模型,峰浓度值分别为1.511、.772、.132、.022、.72μg/mL,AUC分别为48.456、0.22、52.41、66.045、9.8(μg.h)/mL。比较而言,得米先20%药动学最好,其次为产品C,产品B最差。     

Pharmacokinetics of Amoxicillin Trihydrate in Desert Sheep and Nubian Goats

The pharmacokinetics of amoxicillin were studied in five Desert sheep and five Nubian goats after intravenous (i.v.) or intramuscular (i.m.) administration of a single dose of 10 mg/kg body weight. Following i.v. injection, the plasma concentration-versus-time data were best described by a two-compartment open model. The kinetic variables were similar in both species except for the volume of the central compartment (V_c), which was larger in sheep (p<0.05). Following i.m. injection, except for the longer half-life time of absorption in goats (p<0.05), there were no significant differences in other pharmacokinetic parameters between sheep and goats. The route of amoxicillin administration had no significant effect on the terminal elimination half-life in either species. The bioavailability of the drug (F) after i.m. administration was high (>0.90) in both species. These results indicate that the pharmacokinetics of amoxicillin did not differ between sheep and goats; furthermore, because of the high availability and short half-life of absorption, the i.m. route gives similar results to the i.v. route. Therefore, identical intramuscular and intravenous dose regimens should be applicable to both species.     

我国蒙古羊系统主要地方绵羊品种遗传分化的研究

应用中心产区典型群简单随机抽样的方法,检测控制湖羊、同羊、滩羊、小尾寒羊和洼地羊的血液酶和其他蛋白质变异的5个结构基因座位(Tf、X-p、Ary-Es、Hb-β、Ke)上的遗传变异,引用国内外学者以相同实验方法获得的其他分布于我国周边国家和地区的11个绵羊品种作为分析背景,对16个群体进行遗传距离分析及亲缘关系聚类。结果表明:中亚以东南绵羊群体可以划分为蒙古羊、藏羊和南亚-东南亚羊三大集团,湖羊、同羊、滩羊、小尾寒羊和洼地羊均属于"蒙古羊"系统。     

基于mt DNA D-loop区序列的野绵羊与新疆地方绵羊的系统发育研究

为研究新疆绵羊的起源以及野生绵羊对新疆地方绵羊品种的遗传贡献,采用生物信息学的方法研究野生绵羊与新疆地方家绵羊的亲缘关系,结果表明:塔什库尔干羊、巴什拜羊、哈萨克羊均起源A、B、C三个世系,与东方盘羊关系较近,而和田羊、阿勒泰羊单独聚为一类,可能为D进化支,且与盘羊关系较近。     

盐酸贝那普利咀嚼片在犬体内的生物等效性研究

为研究国产和进口盐酸贝那普利片在犬体内的药代动力学和生物等效性,将20只健康比格犬随机分成2组,采用双周期交叉试验设计,按0.5 mg/kg体重分别单剂量口服受试产品和参比产品。采用UPLC-MS/MS法测定血浆中盐酸贝那普利及贝那普利拉的浓度,利用WinNonlin5.2.1软件计算主要药动学参数,并评价两种产品的生物等效性。结果显示,受试产品和参比产品中盐酸贝那普利Tmax分别为（0.85±0.36）h和（0.98±0.40）h;Cmax分别为（65.85±31.14）ng?mL-1和（52.02±25.79）ng?mL-1;AUC0-t分别为（46.98±29.77）h?ng?mL-1和（40.54±20.76）h?ng?mL-1;AUC0-∞分别为（48.28±30.05）h?ng?mL-1和（41.54±20.85）h?ng?mL-1;受试产品和参比产品的贝那普利拉Tmax分别为（1.78±0.55）h和（1.90±0.72）h;Cmax分别为（63.05±28.44）ng?mL-1和（55.29±36.01）ng?mL-1;AUC0-t分别为（249.09±87.90）h?ng?mL-1和（212.50±90.03）h?ng?mL-1;AUC0-∞分别为（274.15±93.86）h?ng?mL-1和（264.42±161.86）h?ng?mL-1。受试产品和参比产品的Tmax、Cmax、AUC0-t和AUC0-∞均无显著性差异（P>0.05）。双单侧t检验及90%置信区间结果均提示两种制剂生物等效,临床上可相互替代。该试验为兽医临床安全使用该药提供科学的依据。     

青海绵羊血清铁传递蛋白的电泳研究

采用聚丙烯酰胺凝胶电泳法对青海省５个品种共１０５０只绵羊的血清铁传递蛋白进行了电泳研究。结果发现青海绵羊的血清运铁蛋白共有１１个电泳变异体（Ｉ，Ａ，Ｇ，Ｂ，Ｌ，Ｃ，Ｄ，Ｍ，Ｅ，Ｑ，），构成３７种电泳表型（ＩＡ，ＡＥ，ＡＡ，ＡＧ，ＡＢ，ＡＬ，ＡＣ，ＡＤ，ＡＭ，ＡＥ，ＡＢ，ＧＧ，ＧＢ，ＧＬ，ＧＣ，ＧＤ，ＧＭ，ＧＱ，ＢＢ，ＢＣ，ＣＤ，ＣＭ，ＬＣ，ＬＤ，ＬＥ，ＣＣ，ＣＤ，ＣＭ，ＣＥ，ＣＱ，ＣＰ，ＤＤ，ＤＭ，ＤＥＤＱ，ＫＰ，ＭＱ）。在５个品种绵羊中，藏羊血清铁传递蛋白的电泳变异体和电泳表型最多，分别为１１个和２８种，茨盖羊的最少，分别为６个和１６种，青海细毛羊，新疆细毛羊和青海半细胞毛羊介于两者之间。     

牛奶中土霉素残留检测方法改进及临床消除规律探究

试验对牛奶中的土霉素残留检测方法进行了改进,并采用改进后的方法对牛奶中土霉素的临床消除情况进行了探究。样品前处理过程中,选取0.1mol/LNa₂EDTA-Mcllvaine缓冲溶液提取牛奶中的土霉素,正己烷除脂及HLB固相萃取柱净化浓缩。釆用Symmetry Shield RPC18(250mm×4.6mm,5μm)反相色谱柱,以乙腈和0.048%的磷酸溶液(pH2.5)为流动相,采用梯度洗脱的方式对样品进行分析。方法改进后,土霉素的出峰时间为6.5min,峰形尖锐,与样品中的杂质峰分离良好。土霉素标准溶液在5~2000μg/kg范围内线性关系良好,标准曲线R²=0.9999;牛奶中土霉素在10、20、100μg/kg3组浓度的加标回收率分别为87.9%、90.5%和87.8%,批内变异系数范围为2.2%~5.8%,批间变异系数范围为4.0%~5.1%。土霉素在牛奶中的检出限为5μg/kg,定量限为10μg/kg,适用于研究土霉素在牛奶中的残留消除规律。选取了29头产后患有子宫内膜炎的奶牛,分成4个不同剂量组(2、3、4和5g),通过子宫内灌注土霉素的方式进行治疗,然后采用优化后的方法检测牛奶中残留的土霉素。结果发现,4g及以下剂量组给药72h后,牛奶中的土霉素可以消除至残留限量以下;而当给药剂量达到5g时,72h后牛奶中的土霉素未消除至残留限量以下,因此不建议采用5g及以上剂量灌注病牛子宫。     

青海细毛羊,新疆细毛羊和藏系绵羊染色体比较研究

采用外周血微量全血培养法研究了生活在青海省三角城种羊场的青海细毛羊、新疆细毛羊、藏系绵羊的染色体核型及畸变。结果表明：三种绵羊二倍体细胞的染色体数目均为２ｎ＝５４，ＮＦ＝６２，公羊核型为５４，ＸＹ；母羊为５４，ＸＸ。染色体畸变类型主要为结构断裂和多倍体，其频率分别为：青海细毛羊１．５３０％和１．８４４％；新疆细毛羊２．２９２％和１．５６８％；藏系绵羊２．０２２％和１．１０３％，并对三种羊的畸变类型进行下检验，结果差异均为极显著（Ｐ＜０．０１）。     

Study on Optimizations of Oxytetracycline Residues Detection Method in Milk and its Clinical Elimination

Here an improved HPLC-PAD method was developed and demonstrated suitable for studying the clinical residue elimination of oxytetracycline in milk from postpartum cows with uterine diseases after intrauterine treatment with oxytetracycline.In this study, 0.1 mol/L Na₂EDTA-Mcllvaine buffer solution was used to extract oxytetracycline from milk, n-hexane for degreasing, and a 3 CC Oasis HLB solid-phase extraction column for purification and concentration.A reversed phase chromatographic column Symmetry Shield RP C18 (250 mm×4.6 mm, 5 μm) with acetonitrile and 0.048% phosphoric acid solution (pH 2.5) as mobile phase by gradient eluting was applied to as the chromatographic separation condition.The results showed that the retention time of oxytetracycline was 6.5 min with a symmetrical and sharp peak, which was well separated from the impurity in the milk sample.Oxytetracycline standard solutions within the concentrations ranging from 5 to 2 000 μg/kg, had a good linearity between peak areas and the concentrations, R²=0.9999.The recoveries of oxytetracycline at three levels of 10, 20, 100 μg/kg were 87.9%, 90.5% and 87.8%, respectively, with the coefficient of variation ranged from 2.2% to 5.8% in intra-day and 4.0% to 5.1% in inter-day.The LOD was 5 μg/kg and the LOQ was 10 μg/kg.All of those parameters suggested that the optimized method was suitable for the study on the clinical residue elimination of oxytetracycline.29 postpartum cows with uterus disease were randomly divided into four different groups in terms of dosage, 2, 3, 4 and 5 g, and treated with oxytetracycline by intrauterine infusion administration, and the residues of oxytetracycline in milk were detected to study its clinical residue elimination.The results showed the oxytetracycline in milk fell to the MRL during 72 h after treatment at 4 g and below dose group.However, in 5 g dose group, residue levels of oxytetracycline in milk were above the MRL at 72 h after treatment.Therefore, 5 g and the higher were not recommended for intrauterine infusion administration.     

土霉素注射液在猪体内药代动力学比较

对长效土霉素注射液进行了猪体内药代动力学的比较研究。试验将三种产品（Ａ、Ｂ、Ｃ）分别一次肌肉注射猪３头,剂量２０ｍｇ／ｋｇ。结果表明,消除半衰期以产品Ｂ最长,血药峰浓度以产品Ｂ最高,达到峰浓度时间以产品Ａ最慢,药时曲线下面积以产品Ｂ最大,２４小时血药浓度以产品Ｂ最高,４８小时血药浓度以产品Ｃ最低。以血浆土霉素浓度０．５μｇ／ｍｌ为最小有效浓度,产品Ａ和Ｂ能够维持有效血药浓度２４小时,产品Ｃ仅能够维持有效血药浓度１２小时。