丙硫咪唑在鸡体内的药代动力学及组织残留的研究

给鸡单剂量口服丙硫咪唑(15mg/kg),用HPLC法测定不同时间的鸡体内药物及其代谢物的浓度.结果,在血浆和组织中均未发现丙硫咪唑,而其两个代谢物丙硫咪唑亚砜(亚砜)和丙硫咪唑砜(砜)在血浆中的药代动力学行为符合方程:C(亚砜)=22.3581(e~(-0.142(t-0.6053))-e~(-0.4505(t-0.8053)));C(砜)=4951.7774(e~(-0.2769(t-0.9111))-e~(0.278(t-0.9111)))。亚砜和砜的主要药动学参数分别为:消除相半衰期(t1/2ke)为4.87和2.57h,表观分布容积(Vd)为0.98和0.76L/kg,峰时间(Tm)为4.34和4.52h,峰浓度(Cm)为8.98和7.22μg/mL。亚砜在心、肝、胰、肺、肾等组织中的残留量:给药后3d分别为1.14、5.35、2.42、1.78、2.45μg/g;5d分别为0.281.79、2.34、1.13、1.16μg/g;7d分别为0.12、0.68、1.69、0.48、0.69μg/g.砜在上述组织中的残留量:给药后3d分别为3.15、10.44、8.16、0.99、2.83μg/g;5d分别为1.53、1.04、4.11、0.86、0 89μg/g;7d分别为:0.77、0.67、2.09、0.53、0.12μg/g。     

冬季驱除幼年牦牛寄生蠕虫技术的示范效益观察

在对幼年牦牛寄生蠕虫动态和防治研究的基础上,于1990年1月选用50g/l的丙硫咪唑混悬液,按10mg/kg和20mg/kg剂量投服后剖检15头结果:试验组平均荷虫数比对照组低96.8—99.3％,驱虫效果显著。同年2月按15mg/kg剂量对1336头幼年牦牛驱虫,5月下旬调查试验组牦牛春乏死亡率(1.1％)比对照组(8.45％)下降7.35个百分点,比前三年(1987—1989)平均(6.3％)下降5.2个百分点,证明丙硫咪唑混悬液安全性良好,使用方便,生产效益显著。     

蒲公英中总黄酮正交提取工艺的建立

考察pH值、浸泡时间、料液比对蒲公英总黄酮提取率的影响,建立蒲公英总黄酮提取工艺。色谱柱:Eclipse×DB-C_(18)柱(4.6 mm×250 mm,5μm);流动相:甲醇-冰醋酸(60∶40)(V/V);柱温:30℃;流速:1.0 mL/min;检测波长:254 nm;进样量:20μL,测定黄酮的总含量。结果表明,各因素影响力大小为:pH值浸泡时间料液比;蒲公英中黄酮提取率为9.26%,结果准确可靠。     

高效液相-串联质谱法测定蜂蜜中利巴韦林残留研究

本研究采用同位素内标法建立了蜂蜜中利巴韦林残留液相色谱-串联质谱方法。样品经提取后经混合型阳离子交换固相萃取净化后上机测定,色谱柱为Hypercarb多孔石墨碳色谱柱(100 mm×2.1 mm,5μm),以0.1%(V/V)甲酸甲醇-0.1%(V/V)甲酸水为流动相进行梯度洗脱,采用电喷雾正离子(ESI⁺)和多反应监测(MRM)模式测定,同位素内标法定量。结果显示,利巴韦林进样浓度在2～100 ng/mL浓度范围内呈良好的线性关系(R²=0.9995);方法检出限和定量限分别为1μg/kg和2μg/kg;2、4、20μg/kg三个添加水平下,回收率在67.6%～112.7%之间,批内、批间相对标准偏差均小于15%。本方法简便、准确、快速、灵敏,适用于蜂蜜中利巴韦林残留检测。     

肥育猪丙硫咪唑中毒的诊断

丙硫咪唑即丙硫苯咪唑 (Albendazole) ,又名阿苯哒唑、抗蠕敏 ,是苯丙咪唑 (Benzim idazole)的衍生物 ,是一种新型的高效、广谱、低毒的苯咪唑类抗蠕虫药。该药品被猪体吸收后 ,在猪肝细胞微粒体内 ,右微粒体酶代谢 ,其代谢的中间产物是丙硫咪唑砜和丙硫咪唑亚砜 ,最终产物是二氨基亚砜。这些代谢产物随血液循环分布到各组织器官中 ,从而杀死寄生虫。丙硫咪唑口服后机体极易吸收 ,建议口服驱虫剂量为每千克体重 1 0～30mg。 2 0 0 2年 8月 4日青海省西宁市某猪场发生了一次因不按说明操作 ,导致猪群发生丙硫咪唑中毒的恶性事件 ,现报道如下…     

用反相高效液相色谱-紫外检测法测定桑叶中芦丁、槲皮素和1-脱氧野尻霉素的含量

为高效检测桑叶中的药用活性成分,进行了用反相高效液相色谱-紫外检测法(RP-HPLC-UV)综合测定桑叶中芦丁、槲皮素和1-脱氧野尻霉素(1-DNJ)含量的试验。采用85%乙醇超声辅助萃取桑叶中的芦丁和槲皮素,以0.05 mol/L HCl为溶剂提取1-DNJ,并在pH8.5的硼酸盐缓冲液中进行衍生化反应,生成具有紫外吸收的1-DNJ-FMOC络合物。色谱柱为Alltima C18(4.6 mm×250 mm,5μm),检测波长分别为360、360、254 nm,流动相分别为V(四氢呋喃)∶V(0.02%磷酸)=25∶75、V(乙腈)∶V(pH4.0、0.5 mol/L醋酸缓冲液)=27∶73、V(乙腈)∶V(0.1%醋酸)=36∶64。检测结果显示:芦丁、槲皮素和1-DNJ的色谱图分离效果良好,峰面积与浓度呈高度正相关,回收率(n=3)分别为99.14%、98.89%、100.85%,相对标准偏差(RSD)分别为1.01%、0.33%、1.24%。试验显示建立在以上条件下的检测方法精密度高,检测结果准确可靠。     

正相液相色谱法测定饲料添加剂天然维生素E中的生育酚和生育三烯酚的含量

天然维生素E因具有促进动物生长、提高肉品质等功能,已被逐步用于宠物及畜禽饲养,但行业中尚无规范该类饲料及饲料添加剂产品的标准及检测方法。本研究旨在建立采用正相液相色谱-紫外检测器(NPLC-UV)测定饲料添加剂中8种天然维生素E含量的分析方法。样品经甲醇浸润后,以乙酸乙酯/正己烷(3∶97,V/V)为提取溶剂在室温下进行超声浸提。使用Kromasil 60-5 diol(4.6 mm×150 mm)色谱柱进行分离,正庚烷/四氢呋喃(100∶4,V/V)等度洗脱,流速1.0 mL/min,柱温40℃,紫外检测波长为292 nm。结果表明:生育酚和生育三烯酚含量在0.2～50.0μg/mL时线性关系良好(R2≥0.999 0),方法定量限为0.01%,加样平均回收率为81.3%～109.8%,相对标准偏差(RSD)小于7.9%。通过对实际样品测定,该方法操作简单,结果准确可靠,有助于规范天然维生素E饲料产品市场。     

鱼肌肉中磺胺二甲嘧啶及其代谢产物的高效液相色谱法测定

研究了鲟鱼肌肉中磺胺二甲嘧啶及其主要代谢物N4 乙酰化磺胺二甲嘧啶的高效液相色谱测定法。样品用乙腈提取,正己烷脱脂,碱性氧化铝SPE柱净化,高效液相色谱 Inertsil ODS 3(4 6 mm×250 mm, 粒径 5μm),流动相:水 乙腈 乙酸(76∶24∶0 05, V/V/V)测定。在 20、100、2 000μg/kg 的添加浓度,测得 SM2、N4 ACE SM2 的平均回收率范围分别为80 4%~85.3%、88.4%~96.0%;2种药物的检测限均为10μg/kg。     

兽用丙硫咪唑片剂质量检测

对陕西、甘肃、青海三省部分厂家生产的兽用丙硫咪唑片剂进行了质量检测，结果发现兽用丙硫咪唑片平均标示量青海省为９５．６３％，陕西省为９１．４１％，均系合格产品，而甘肃省的为７６．８６％，属不合格产品。     

高效液相色谱法检测蜂蜜中替硝唑药物残留研究

研究建立蜂蜜中替硝唑残留量的高效液相色谱测定方法。样品经12mL乙酸乙酯液液萃取、净化,在317nm波长下用二极管矩阵检测器检测。色谱柱为Agela Venusil ASB-C18(4.6×250mm,5μm),流动相甲醇∶水为17∶83(V/V),流速1.0mL/min。替硝唑浓度在0.10～4.00μg/mL范围内与峰面积呈良好的线性关系。平均回收率为82.3%～90.0%,相对标准偏差为2.27%～5.08%,方法的最低检测限10.0μg/kg。     

阿苯达唑对波尔山羊消化道线虫的药效试验

为了观察阿苯达唑片对波尔山羊消化道线虫的驱除效果,探讨其对波尔山羊线虫病治疗的最佳剂量,将150只波尔山羊随机分成5组,其中设阿苯达唑7.5、15、30 mg/kg作为试验组,同时设左旋咪唑7.5 mg/kg作为药物对照组和阳性对照组,给药前后检查虫卵和虫体,计算虫卵转阴率、虫卵减少率和驱虫率,最后进行统计分析。结果显示,高剂量组和中剂量组的虫卵转阴率、虫卵减少率和驱虫率均显著高于低剂量组和盐酸左旋咪唑片对照组(P0.01),而高剂量组与中剂量组的虫卵转阴率、虫卵减少率和驱虫率差异不显著。15 mg/kg的阿苯达唑片对波尔山羊线虫的驱除效果安全。     

基于HPLC法测定五氯柳胺阿苯达唑复方混悬液中的有关物质

试验旨在通过高效液相色谱（high performance liquid chromatography,HPLC）法测定五氯柳胺阿苯达唑复方混悬液的有关物质。采用高效液相色谱法,以自身对照法计算五氯柳胺阿苯达唑复方混悬液有关物质的量。选用Thermo Hypersil BDS C18色谱柱（4.6 mm×150 mm,5 μm）;流动相以0.1%磷酸-10 mmol/L磷酸二氢铵水溶液为A相,以甲醇为B相,31：69（V/V）;流速为1 mL/min;进样量为5 μL;柱温30℃;检测波长295 nm。结果显示,在建立的色谱条件下,五氯柳胺阿苯达唑复方混悬液中的主成分峰与杂质峰均能基线分离。3,5,6-三氯水杨酸、2-氨基-4,6-二氯苯酚盐酸盐、五氯柳胺、阿苯达唑在5~100 μg/mL内与峰面积线性关系良好（R² ≥ 0.999）,定量限分别为5 μg/mL及750、500、225 ng/mL,检测限分别为1 μg/mL及500、250、100 ng/mL,杂质3,5,6-三氯水杨酸、2-氨基-4,6-二氯苯酚盐酸盐总平均回收率分别为101.15%、100.35%,总平均回收率RSD均为0.71%（n=9）。经方法学验证,建立的HPLC方法简单、快速、准确,可用于五氯柳胺阿苯达唑复方混悬液中有关物质的测定。     

Enhanced Plasma Availability of the Metabolites of Albendazole in Fasted Adult Sheep

Lifschitz, A., Virkel G., Mastromarino, M. and Lanusse C., 1997. Enhanced plasma availability of the metabolites of albendazole in fasted adult sheep. Veterinary Research Communications, 21 (3), 201-211The influence of fasting prior to treatment and of dosing rate on the plasma availability and disposition kinetics of albendazole (ABZ) and its sulphoxide (ABZSO) and sulphone (ABZSO2) metabolites was studied in adult sheep grazing on pasture. A micronized suspension of ABZ was administered orally at either 7.5 mg/kg (group A) or 11.3 mg/kg (group C) to sheep fed ad libitum, and at 7.5 mg/kg to sheep subjected to a 24 h fasting period prior to treatment (group B). Blood samples were taken serially over 96 h after treatment, and the plasma was analysed for ABZ and its metabolites by high-performance liquid chromatography. ABZSO and ABZSO2 were recovered from the plasma. Fasting induced marked modifications in the pharmacokinetic behaviour of the ABZ metabolites in sheep. An extended absorption process, with a delayed peak concentration in the plasma, was observed for both metabolites in the fasted sheep. Significantly higher area under the curve (AUC) and peak plasma concentration (Cmax) values were obtained for both metabolites in the fasted animals compared to those fed ad libitum. Delayed elimination with prolonged detection in plasma was also observed in the fasted sheep. Treatment with ABZ at 7.5 mg/kg in the starved animals resulted in bioequivalence to the administration of the compound at a 50% higher dose rate (11.3 mg/kg) in the fed animals. It is suggested that fasting enhances ABZ dissolution and absorption by delaying its passage down the digestive tract.     

Determination of the Anthelmintic Efficacy of Albendazole in the Treatment of Chickens Naturally Infected with Gastrointestinal Helminths

In the spring of 2006, 60 naturally infected hens obtained from a broiler-breeder farm in northwest Arkansas were used in a controlled titration study to determine the anthelmintic efficacy of albendazole in the treatment of both nematode and cestode infections. Albendazole was used at the dose rates of 0.0, 5.0, 10.0, and 20.0 mg/kg of BW, with all treatments given individually as an oral suspension on d 0 (split doses) and with necropsies for parasite collection conducted on d 7. There were 15 birds per treatment group. Statistically significant (P < 0.05) reductions in worm burdens from control levels were seen at the 5.0 mg/kg dose level for adult and larval stages of Ascaridia galli, Heterakis gallinarum, and Capillaria obsignata. A significant (P < 0.05) reduction in the numbers of Raillietina cesticillus (scolexes) from control group levels was seen only at the 20.0 mg/kg rate of treatment. For albendazole given at the rates of 5.0, 10.0, and 20.0 mg/kg, respective anthelmintic efficacies based on geometric means were 87.7, 91.2, and 98.2% (A. galli larvae); 100.0, 100.0, and 100.0% (A. galli adults); 96.9, 95.7, and 98.9% (H. gallinarum larvae); 92.7, 95.4, and 94.9% (H. gallinarum adults); 90.3, 91.3, and 95.1% (C. obsignata larvae and adults combined); and 73.1, 73.1, and 96.2% (R. cesticillus). No adverse reactions to albendazole were observed in this study.     

阿苯达唑对自发性兔脑炎原虫病的治疗

为了有效地治疗兔脑炎原虫病,本研究根据脑炎原虫的生物学特点和对组织损伤的特征选用阿苯达唑进行了治疗试验。将28只3～4月龄隐性感染的獭兔,随机分为对照组和治疗组进行试验。治疗组按30mg／kg剂量（首次给药量为50mg／kg）,每隔12h给药1次,连续用药10d,停药1周为1个治疗期,共治疗3个疗程。对照组按正常饲养。每1疗程之后,均采血和尿液进行ELISA检测和尿沉渣虫体检查。结果,治疗组的病兔用阿苯达唑治疗3个疗程后,ELISA检测的D值均低于标准值（〈0．044）,即抗脑炎原虫血清抗体呈阴性反应,从尿沉渣中也不能检出虫体。而对照组病免的D值则大大高于正常值．从尿沉渣中均易检出虫,并有1只对照兔出现典型的神经症状,剖检后从脑组织中检出脑炎原虫性肉芽肿。经方差分析,2组间差异非常显著（P〈0．01）。试验证明,阿苯达唑对兔脑炎原虫有良好治疗作用,用药的时机以脑炎原虫还未进入脑组织时最合适,用药的剂量一定要保持有效的杀虫浓度。     

The Pharmacokinetics and Efficacy of Long-Term Low-Level and Split-Dose Administration of Albendazole Through In-Feed Formulations against Ovine and Caprine Parasitic Gastroenteritis

Two trials were conducted against natural and experimentally induced parasitic gastroenteritis in sheep and goats using an in-feed formulation of albendazole to evaluate its therapeutic and prophylactic efficacy. In the first trial, albendazole was incorporated in feed pellets to deliver an average daily dose of 0.7 mg/kg body weight in order to evaluate its prophylactic efficacy. In the second trial, feed pellets were offered to deliver an average total dose of 8.0 mg/kg body weight in two equal split doses in order to evaluate its curative efficacy.Sustained plasma concentrations of the active compound, albendazole sulphoxide, and its metabolite albendazole sulphone, sufficient to prevent establishment of infection, were achieved when the animals were allowed to feed on medicated pellets for 10 consecutive days. The bioavailability of the metabolites of albendazole following the administration of a therapeutic dose in two split doses of the in-feed formulation was sufficient to remove established adult nematodes. The concentrate feed pellets could be used for self-medicating small ruminants for therapeutic use as well as for prophylaxis based on their strategic use appropriate to the epidemiology of the parasitic disease.     

Plasma Disposition and Faecal Excretion of Netobimin Metabolites and Enantiospecific Disposition of Albendazole Sulphoxide Produced in Ewes

Netobimin (NTB) was administered orally to ewes at 20 mg/kg bodyweight. Blood and faecal samples were collected from 1 to 120 h post-treatment and analysed by high-performance liquid chromatography (HPLC). Using a chiral phase-based HPLC, plasma disposition of albendazole sulphoxide (ABZSO) enantiomers produced was also determined. Neither NTB nor albendazole (ABZ) was present and only ABZSO and albendazole sulphone (ABZSO₂) metabolites were detected in the plasma samples. Maximum plasma concentrations (C<_max) of ABZSO (4.1 ± 0.7 μg/ml) and ABZSO₂ (1.1 ± 0.4 μg/ml) were detected at (t _max) 14.7 and 23.8 h, respectively following oral administration of netobimin. The area under the curve (AUC) of ABZSO (103.8 ± 22.8 (μg h)/ml) was significantly higher than that ABZSO₂(26.3± 10.1 (μg h)/ml) (p<0.01). (−)−ABZSO and (+)-ABZSO enantiomers were never in racemate proportions in plasma. The AUC of (+)-ABZSO (87.8±20.3 (μg h)/ml) was almost 6 times larger than that of (−)−ABZSO (15.5 ±5.1 (μg h)/ml) (p < 0.001). Netobimin was not detected, and ABZ was predominant and its AUC was significantly higher than that of ABZSO and ABZSO₂, following NTB administration in faecal samples (p > 0.01). Unlike in the plasma samples, the proportions of the enantiomers of ABZSO were close to racemic and the ratio of the faecal AUC of (−)−ABZSO (172.22 ±57.6 (μg h)/g) and (+)-ABZSO (187.19 ±63.4 (μg h)/g) was 0.92. It is concluded that NTB is completely converted to ABZ by the gastrointestinal flora and absorbed ABZ is completely metabolized to its sulphoxide and sulphone metabolites by first-pass effects. The specific behaviour of the two enantiomers probably reflects different enantioselectivity of the enzymatic systems of the liver that are responsible for sulphoxidation and sulphonation of ABZ.     

Aspects of the Pharmacokinetics of Albendazole Sulphoxide in Sheep

The plasma disposition kinetics of albendazole sulphoxide (ABZSO), ((+)ABZSO and (–)ABZSO) and its sulphone metabolite (ABZSO₂) were investigated in adult sheep. Six Corriedale sheep received albendazole sulphoxide by intravenous injection at 5 mg/kg live weight. Jugular blood samples were taken serially for 72 h and the plasma was analysed by high-performance liquid chromatography (HPLC) for albendazole (ABZ), ABZ sulphoxide (ABZSO) and albendazole sulphone (ABZSO₂). Albendazole was not detected in the plasma at any time after the treatment, ABZSO and ABZSO₂ being the main metabolites detected between 10 min and 48 h after treatment. A biexponential plasma concentration versus time curve was observed for both ABZSO and ABZSO₂ following the intravenous treatment. The plasma AUC values for ABZSO and ABZSO₂ were 52.0 and 10.8 (g.h)/ml, respectively. The ABZSO₂ metabolite was measurable in plasma between 10 min and 48 h after administration of ABZSO, reaching a peak concentration of 0.38 g/ml at 7.7 h after treatment. Using a chiral phase-based HPLC method, a biexponential plasma concentration versus time curve was observed for both ABZSO enantiomers. The total body clearance was higher for the (–) than for the (+) enantiomer, the values being 270.6 and 147.75 (ml/h)/kg, respectively. The elimination half-life of the (–) enantiomer was shorter than that of the (+) enantiomer, the values being 4.31 and 8.33 h, respectively. The enantiomeric ratio (+)ABZSO/(–)ABZSO at t ₀ was close to unity. However, the ratio in the plasma increased with time.     

Influence of Diet Type and Pretreatment Fasting on the Disposition Kinetics of Albendazole in Sheep

The influence of the quality and quantity of diets on the disposition kinetics of albendazole were studied in sheep in two different experiments. The plasma concentration profiles of albendazole sulphoxide and albendazole sulphone were measured following intraruminal administration of albendazole at 5.0 mg/kg body weight in weaner sheep offered three different diets: 100% green Sorghum spp., 100% dry mature Cenchrus ciliaris hay and a 50:50 mix of these two diets. The peak plasma concentrations and the availability of the albendazole metabolites, as measured by the area under the concentration–time curve, were significantly higher (p<0.01) in the animals offered exclusively dry fodder compared to other diets. Changing the diet from dry to green fodder resulted in a significantly lower systemic availability of the drug metabolites. It is suggested that a decreased transit time of the digesta in the bowel on the green diet, with its high water content, limited the systemic availability of the drug by reducing the time available for gastrointestinal absorption.An experiment on the influence of different levels of pretreatment fasting on the pharmacokinetics of albendazole revealed significantly higher (p<0.05) plasma concentrations of the anthelmintically active sulphoxide metabolite from 12 h onwards following administration of the drug in animals subjected to 24 h of pretreatment fasting compared to other groups with pretreatment fasting of 8, 12 or 18 h. The area under the concentration–time curve and the minimum residence time of the drug metabolites were significantly greater (p<0.05) in animals that had been fasted for 24 h. It is suggested that fasting induces a decrease in the flow of digesta through the gastrointestinal tract of ruminants and prolongs the duration of dissolution of the drug, resulting in enhancement of the absorption of albendazole and of the systemic availability of its metabolites.     

虫卵孵化试验对某羊场羊线虫抗药性的检测

为了解家畜寄生线虫对使用较久的驱虫药丙硫咪唑的抗药性情况, 用虫卵孵化试验对江苏某羊场进行抗药性检测, 测得丙硫咪唑虫卵孵化半数抑制量ＩＤ５０ ＝ ０－０６０ ２ μｇ／ｍＬ, 约是敏感株（０－０２０ ４ μｇ／ｍＬ） 的３ 倍, 但较世界兽医寄生虫促进协会提出的线虫抗药性临界值（０－１ μｇ／ｍＬ） 小。虫卵减少试验也证实了该羊场不存在抗药性。因此该场羊寄生线虫尚无抗药性。