吡喹酮单独和联合狂犬弱毒疫苗对家兔给药后血浆药物动力学研究

为测定单独给药及联合狂犬弱毒疫苗制剂给药后家兔血浆的血药浓度,建立了以乙腈/水为流动相进行梯度洗脱的HPLC方法测定血浆中吡喹酮的含量,并初步研究其药代动力学特点。实验组分为对照组(生理盐水)、7%吡喹酮注射剂组与狂犬疫苗-吡喹酮复合制剂组,空腹12 h后肌注,在给药后不同时间点耳廓静脉采血,处理血样后HPLC测定。采用DSA软件处理血药浓度数据的药代动力学参数。吡喹酮峰保留时间在15.10 min、无杂峰干扰,且拖尾因子和塔板数均符合要求,HPLC方法学验证表明吡喹酮的标准曲线在2~16μg/mL范围内线性良好(R²=0.9996),其稳定性、重复性及加样回收率均符合生物样品测定要求。狂犬弱毒疫苗-吡喹酮复合制剂给药后,血浆中吡喹酮含量的变化趋势与吡喹酮单独给药呈现相似的代谢规律,即15 min后迅速增加,在1 h达到峰值,4 h含量达到低值,此后代谢缓慢,在24 h仅能检测到微量吡喹酮。通过研究单独和联合狂犬弱毒疫苗制剂给药后家兔血浆中吡喹酮的药代动力学过程,初步阐明了其体内药物吸收和代谢过程,为临床安全合理给药提供参考。     

吡喹酮注射剂早期治疗小鼠血吸虫病效果的初步研究

为探索吡喹酮新制剂早期治疗血吸虫病效果,对人工感染日本血吸虫20d的小鼠皮下给药进行减虫率、肝脏减卵率统计,并在不同时间点对口服组和皮下注射吡喹酮新制剂组的未感染小鼠在给药后采集血浆,高效液相色谱法建立药时曲线。结果显示新制剂600mg/kg剂量治疗的3次试验的减虫率分别为72.88%、82.69%和56.7%,肝脏减卵率分别为81.7%、94.8%和70.7%,对感染20d期别的血吸虫有较好效果。而高效液相色谱法检测血药浓度显示,新制剂经皮下给药方式可使有效杀虫浓度(约0.3μg/mL)持续10d以上,具有缓释作用。吡喹酮新注射制剂能杀灭20d童虫,减少血吸虫病的危害,对血吸虫病的防治有较大的意义。     

猫经口内服2种米尔贝肟吡喹酮片的药代动力学比较研究

本试验将16只成年健康猫随机分成2组,每组8只(公母各半),采用单剂量随机平行对照试验设计,分别单剂量(4 mg/kg体重,以米尔贝肟计)经口内服国产(受试品)和进口(对照品)米尔贝肟吡喹酮片,进行其在猫体内的药代动力学比较研究.给药后按预定时间采集血样,采用HPLC法进行血浆中米尔贝肟和吡喹酮含量的测定,实测血药浓度—时间数据采用Winnonlin 5.2药代动力学分析软件计算药代动力学参数.结果显示,米尔贝肟吡喹酮片对照品单剂量内服后,米尔贝肟的消除半衰期(T_1/2β)为(20.08±7.57)h,达峰时间(T_max)和峰值浓度(C_max)分别为6.00 h和(764.43±251.40)ng/mL,平均曲线下面积(AUC)为(15.00±5.05)ng/(L·h),平均滞留时间(MRT)(18.60±1.52)h;吡喹酮的消除半衰期(T_1/2β)为(6.27±5.26)h,达峰时间(T_max)和峰值浓度(C_max)分别为(3.88±0.35)h和(1018.25±200.19)ng/mL,平均曲线下面积(AUC)为(8.69±2.07)ng/(L·h),平均滞留时间(MRT)(6.56±1.07)h.米尔贝肟吡喹酮片受试品单剂量内服后,米尔贝肟的消除半衰期(T_1/2β)为(15.07±4.05)h,达峰时间(T_max)和峰值浓度(C_max)分别为(5.25±1.04)h和(806.65±299.01)ng/mL,平均曲线下面积(AUC)为(15.18±5.97)ng/(L·h),平均滞留时间(MRT)(17.47±1.97)h,相对生物利用度为101.20%;吡喹酮的消除半衰期(T_1/2β)为(11.11±4.62)h,达峰时间(T_max)和峰值浓度(C_max)分别为(5.25±1.04)h和(880.47±241.27)ng/mL,平均曲线下面积(AUC)为(9.64±2.76)ng/(L·h),平均滞留时间(MRT)(10.52±1.52)h,相对生物利用度为119.16%.与对照品相比,受试品的药代动力学参数中除米尔贝肟的消除半衰期显著缩短、吡喹酮的达峰时间显著延迟外(P<0.05),其他药代动力学参数差异均不显著(P>0.05).结果表明,猫经口内服米尔贝肟吡喹酮片受试品与对照品后具有相似的药代动力学特征.     

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。     

银翘天甘含药血清制备工艺的优化

本研究通过单因素试验和响应面分析设计优化银翘天甘醇提物制剂含药血清的制备工艺,研究采血时间、给药次数及给药浓度对小鼠血清中绿原酸含量的影响。结果表明,银翘天甘醇提物制剂含药血清最佳制备工艺条件为:给药浓度为0.024 g/mL,给药4次,于最后一次给药后33 min采血。此条件下含药血清中绿原酸含量达到33.34μg/mL。     

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.     

盐酸苯噁唑在鹿体内的药代动力学研究

本研究的主要目的是建立鹿血浆盐酸苯嗯唑浓度反相高效液相色谱紫外检测法,探讨盐酸苯噁唑在鹿血浆中的药代动力学.6只临床健康的梅花鹿,同一环境下饲养后肌内注射盐酸苯恶唑(0.44 mg·kg-1),颈静脉采血8 mL后分离血浆,通过建立的高效液相色谱检测法,测定各采血时间的血浆药物浓度.结果表明,盐酸苯噁唑单剂量肌内注射给药后,药代动力学符合吸收一室模型,药代动力学参数吸收半衰期(t1/2Ka)、消除半衰期(t1/2Ke)分别为(2.09±0.34)、(13.18±0.24)min,血浆药时曲线下面积(AUC0→∞)为(70±3.50)(μg·mL-1)·min,最大血药浓度(Cmax)为(4.70±0.50)μg·mL-1,血药达峰时间(Tpeak)为(12.46±0.12)min.试验结果提示,盐酸苯噁唑在鹿体内吸收快,消除迅速,4 h后血浆中无药物残留.     

国产碘醚柳胺在绵羊体内的药代动力学及组织残留量的研究

给绵羊单剂量口服碘醚柳胺(7.5mg/kg),用HPLC法测定不同时间的血浆药物浓度。结果,碘醚柳胺在血浆中药物代谢动力学符合开放性二室模型,动力学方程为: C_t=208.586 8e~(-0.4756(t-0.5426)) 18.760 5e~(-0.0439(t-0.5426))-227.445e~(-0.5328(t-0.5426))口服碘醚柳胺后,达峰时间(Tmax)为3.698 9±0.197 4d;峰浓度(Cmax)为18.760 5±1.564 6μg/mL;消除半衰期(T(1/2)β)为15.800 6±0.445 7d;曲线下面积(Auc)为459.000 0±62.531 3μg·d/mL。碘醚柳胺在绵羊的肝、肾、胆汁、肌肉中的残留量:停药后28d分别为0.359 9、0.243 2、0.157 9、0.100 0μg/g;停药后50d,肝脏中的残留量为0.100 0μg/g,其它组织中均检测不到;停药后60d,各组织中均无残留。     

诺氟沙星盐酸小檗碱预混剂在眼斑拟石首鱼体内的药代动力学和残留消除规律研究

研究诺氟沙星盐酸小檗碱在眼斑拟石首鱼体内的药代动力学和残留消除规律。在水温28±2℃、盐度28条件下,将诺氟沙星(Norfloxacin,NFLX)盐酸小檗碱(Berberine hydrochloride,BBH)预混剂按450 mg/kg的剂量口灌眼斑拟石首鱼后,其血浆、肌肉、肝脏和肾脏中的药物浓度采用HPLC-MS/MS测定,药时数据用DAS3.0软件分析。结果显示:单剂量口灌给药后,眼斑拟石首鱼血浆中NFLX和BBH的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1.20、1.79 h,血药浓度峰值(Cmax)分别为358.40、144.89μg/L,药时曲线下面积(AUC0-∞)分别为8252.80、6454.52μg/(L·h),消除半衰期(t1/2β)分别为43.26、27.30 h;NFLX和BBH在鱼体各组织中的分布较广,灌服给药后,肌肉、肝脏和肾脏中NFLX和BBH的Cmax分别为418.05、230.76μg/kg;1745.94、901.09μg/kg;1143.45、997.09μg/kg,tp分别为1.5和1.5 h、1.5和2.0 h、1.5和2.0 h,AUC0-∞分别为7682.00、5596.30μg/(kg·h);31236.90、19096.85μg/(kg·h);22593.93、37509.17μg/(kg·h);NFLX和BBH在眼斑拟石首鱼体内消除速度较慢,灌服给药后肌肉、肝脏和肾脏的t1/2β分别为33.41、61.81 h;20.44、15.04 h;30.28、23.43 h。按450 mg/kg剂量连续5 d口灌给药后,眼斑拟石首鱼血浆、肌肉、肝脏、肾脏中的NFLX和BBH残留消除半衰期(t1/2)分别为30.24、33.33 h;40.76、61.60 h;38.68、36.96 h;43.77、59.40 h。以10μg/kg为最高残留限量,肌肉作为食用靶组织,在本试验条件下,建议休药期不得少于12 d。     

氟苯尼考在哺乳猪体内药代动力学研究

目的研究氟苯尼考注射液在哺乳仔猪体内的药物代谢动力学,为临床更加合理使用该药提供理论基础。方法:选取健康哺乳仔猪6头,按15mg/kg.bw肌内注射氟苯尼考,于给药后24h内采集不同时间点血浆样品,用乙酸乙酯进行二次提取,高效液相色谱-DAD检测法测定药物浓度,得到氟苯尼考在哺乳仔猪体内的药-时数据,PKS药动学软件分析得到药动学数据。结果哺乳仔猪肌内注射氟苯尼考后药动学数据符合开放式一级吸收二室模型,其重要药动学数据如下:分布半衰期tl/2α=62.12min,消除半衰期t1/2β=284.84min,药时曲线下面积AUC=75837μg·mL-·1h,tmax=100.00min,Cmax=118.96mg/L。     

Phase I evaluation of CCNU (lomustine) in tumor-bearing cats

1-(2-Chloroethyl)3-cyclohexyl-1-nitrosourea (CCNU) is an alkylating agent in the nitrosourea subclass. A prospective evaluation of CCNU was done to determine the maximally tolerated dosage of CCNU in tumor-bearing cats. Response data were obtained when available. Twenty-five cats were treated with CCNU at a dosage of 50-60 mg/m3 body surface area. Complete hematologic data were available for 13 cats. Neutropenia was the acute dose-limiting toxicity. The median neutrophil count at the nadir was 1,000 cells/microL (mean, 2,433 cells/microL; range, 0-9,694 cells/microL). The time of neutrophil nadir was variable, occurring 7-28 days after treatment, and counts sometimes did not return to normal for up to 14 days after the nadir. Based on these findings, a 6-week dosing interval and weekly hematologic monitoring after the 1st treatment with CCNU are recommended. The nadir of the platelet count may occur 14-21 days after treatment. The median platelet count at the nadir was 43,500 cells/microL. No gastrointestinal, renal, or hepatic toxicities were observed after a single CCNU treatment, and additional studies to evaluate the potential for cumulative toxicity should be performed. Five cats with lymphoma and 1 cat with mast cell tumor had measurable responses to CCNU. Phase II studies to evaluate antitumor activity should be completed with a dosing regimen of 50-60 mg/m3 every 6 weeks.     

Furosemide continuous rate infusion in the horse: evaluation of enhanced efficacy and reduced side effects

Continuous rate infusion (CRI) of furosemide in humans is considered superior to intermittent administration (IA). This study examined whether furosemide CRI, compared with IA, would increase diuretic efficacy with decreased fluid and electrolyte fluctuations and activation of the renin-angiotensin-aldosterone system (RAAS) in the horse. Five mares were used in a crossover-design study. During a 24-hour period, each horse received a total of 3 mg/kg furosemide by either CRI (0.12 mg/kg/h preceded by a loading dose of 0.12 mg/kg IV) or IA (1 mg/kg IV q8h). There was not a statistically significant difference in urine volume over 24 hours between methods; however, urine volume was significantly greater after CRI compared with IA during the first 8 hours ([median 25th percentile, 75th percentile]: 9.6 L [8.9, 14.4] for CRI versus 5.9 L [5.3, 6.0] for IA). CRI produced a more uniform urine flow, decreased fluctuations in plasma volume, and suppressed renal concentrating ability throughout the infusion period. Potassium, Ca, and Cl excretion was greater during CRI than IA (1,133 mmol [1.110, 1,229] versus 764 mmol [709, 904], 102.7 mmol [96.0, 117.2] versus 73.3 mmol [65.0, 73.5], and 1,776 mmol [1,657, 2.378] versus 1,596 mmol [1,457, 1,767], respectively). Elimination half-lives of furosemide were 1.35 and 0.47 hours for CRI and IA, respectively. The area under the excretion rate curve was 1,285.7 and 184.2 mL x mg/mL for CRI and IA, respectively. Furosemide CRI (0.12 mg/kg/h) for 8 hours, preceded by a loading dose (0.12 mg/kg), is recommended when profound diuresis is needed acutely in horses.     

Prevalence of gastric lesions in racing Alaskan sled dogs

Human and equine athletes are reported to have a high prevalence of gastric disease, and anecdotal evidence suggests a similar phenomenon applies to racing sled dogs. To investigate the prevalence of gastric disease in racing sled dogs, we conducted 2 gastroscopy studies on dogs competing in the annual Iditarod Sled Dog Race. A pilot study of dogs that were either dropped from the 2000 Iditarod Sled Dog Race because of illness or that finished the race indicated that, approximately 5 days after competing, 10 of 28 dogs (35%) had endoscopic evidence of gastric ulceration, erosion, or hemorrhage. The next year, an endoscopic study of 73 dogs participating in the 2001 Iditarod race was performed in order to evaluate a larger population of dogs. Data from 70 of these dogs could be used; 34 (48.5%) had ulceration, erosion, gastric hemorrhage, or some combination of these findings. When this group of 70 dogs was compared retrospectively to a control group of 87 dogs presented to the Texas A&M University (TAMU) Veterinary Medical Teaching Hospital, the Iditarod sled dogs had a significantly higher prevalence (P = .049) of gastric lesions. These findings suggest that, similar to athletes of other species, elite canine athletes have an increased prevalence of gastric disease compared to the canine population at large.     

The Epidemiology of Gastrointestinal Nematodes of Dairy Cattle in Central Kenya

The epidemiology of H. placei and of other gastrointestinal nematodes in yearling dairy cattle was examined on two farms in Kiambu District, central Kenya during each of 13 one-month periods from April 1993 to April 1994. On each farm, 32 newly weaned dairy calves were given a single dose of albendazole and then placed on experimental pastures. Twelve of the animals were designated for bi-monthly slaughter (n = 2) and analysis of worm population characteristics and 20 were designated for blood and faecal collection and for weighing. Two parasite-free tracer calves were grazed alongside the weaner calves each month throughout the study period and were also slaughtered for analysis of worm populations. Faecal egg counts, haematological and serum pepsinogen determinations, herbage larval counts, and animal live weight changes were recorded monthly. The study revealed that Haemonchus placei, Trichostrongylus axei, Cooperia spp. and Oesophagostomum radiatum were responsible for parasitic gastroenteritis and that H. placei was the predominant nematode present in the young cattle on both farms. Faecal egg counts from resident cattle and necropsy worm counts revealed that pasture larval levels were directly related to the amount of rainfall. The total worm burdens in the animals were highest during the rainy season (March–June and October–December) and lowest during the dry seasons (July–September and January–February). The very low recovery of immature larvae of H. placei from the tracer calves indicated that arrested development is not a feature of the life cycle of this parasite in central Kenya. The maintenance of the parasite population depended on continuous cycling of infection between the host and the pasture. The agroclimatic conditions of the study area were such that, in general, favourable weather conditions for the development and survival of the free-living stages of gastrointestinal nematodes existed all year round.     

Diversity of Ectoparasites in Sheep Flocks in Sa~o Paulo,Brazil

The occurrence of ectoparasites in sheep flocks is frequently reported but seldom quantified. Sheep production used to be a predominantly family activity in the state of Sa~o Paulo (Brazil), but it began to become a commercial activity in the past decade. Thus, information about the ectoparasites existing in sheep flocks has become necessary. The present data were obtained by means of questionnaires sent to all sheep breeders belonging to the `Associaça~o Paulista de Criadores de Ovinos' (ASPACO; Sa~o Paulo State Association of Sheep Breeders). Response reliability was tested by means of random visits paid to 10.6% of the respondents. Most of the properties (89.5%) reported the presence of one or more ectoparasites. Screw-worm (Cochliomyia hominivorax) was the most frequent ectoparasite (72.5%), followed by bot fly larvae (Dermatobia hominis, 45.0%), ticks (Amblyomma cajennense) and Boophilus microplus, 31.3%) and finally lice (Damalinia ovis, 13.8%). Combined infestations also occurred, the most common one being screw-worm with bot fly larvae (36.0%) followed by bot fly larvae with ticks (13.9%), screw-worm with ticks (9.3%), bot fly larvae with lice (6.9%), and ticks with lice (5.0%). The most common triple combination was screw-worm, bot fly larvae and ticks (12.8%). Breeds raised for meat or wool were attacked by bot fly larvae and ticks more often than other breeds. Lice were only absent from animals of indigenous breeds. The relationships among these ectoparasites are discussed in terms of sheep breeds, flock size, seasonality and the ectoparasitic combinations on the host.     

Evaluation of biohydrogenation rate of canola vs. soya bean seeds as unsaturated fatty acids sources for ruminants in situ

An experiment was conducted to study disappearance of C14 to C18 fatty acids, lag times and biohydrogenation (BH) rates of C18 fatty acids of ground soya bean and canola seeds in situ. Three ruminally fistulated Dallagh sheep were used to determine ruminal BH of unsaturated fatty acids (UFAs). Differences in the disappearance of fatty acids through the bags and lag times were observed between the oilseeds. We saw that the longer the incubation time of the oilseeds in the rumen, the lower the content of C18:2 and C18:3. Significantly higher lag times for both C18:2 and C18:3 were observed in ground canola compared to ground soya bean. BH rates of C18:2 and C18:3 fatty acids in soya bean were three times higher than those of canola. These results suggest that the fatty acid profile of fat source can affect the BH of UFAs by rumen micro‐organisms. So that UFAs of canola had higher ability to escape from ruminal BH. It seems that fatty acid profile of ruminant products is more affected by canola seed compared to soya bean seed.     

Serum biochemical values and mineral element contents of tissues in yaks

Serum biochemical values and the wet weight to dry weight ratios of tissues were determined in yaks in Shandan county of Gansu province. The liver, kidney, heart and muscle contents of seven elements in yaks were also analysed. Most serum biochemical values were similar to those of cattle, camels and sheep, but the calcium concentration was considerably above the normal range for other ruminants. The liver contained the highest concentrations of copper, manganese and cobalt and the kidney of selenium, iron and calcium.Abbreviations Alb albumin - ALT alanine aminotransferase - AST aspartate aminotransferase - BUN blood urea nitrogen - Chol cholesterol - Glob globulin - -GT -glutamyl transpeptidase - IP inorganic phosphorus - TP total protein     

Avian brood parasitism — a growing research area in behavioral ecology (part Ⅱ)

正We are pleased to publish the second special issue on avian brood parasitism and to be responsible guest editors for the two special issues of Chinese Birds (Vol. 3, No. 4, 2012 and Vol. 4, No. 1, 2013), entitled "Avian Brood Parasitism - A Growing Research Area in Behavioral Ecology". The first issue was published in December 2012. The goal of the two special issues is to publish accumulated knowledge and some of the recent developments in     

Internal Parasites and Haematological Values in Cattle Slaughtered in Buea Subdivision of Cameroon

Tropical Animal Health and Production -