国产咪唑苯脲二丙酸盐在牛体内的药代动力学及组织残留

给牛单剂量肌注咪唑苯脲二丙酸盐(2mg/kg)。用紫外分光光度计测出不同时间的血药浓度,并按有吸收一室模型=M(e~(-ket)—e~(-kat))公式,计算出咪唑苯脲的主要药代动力学参数:吸收速率常数(k_a)为2.027h~(-1);清除速率常数(k_e)为0.419h~(-1),峰时间(T~(max))为1.18h;峰浓度(C~(max))为1.746μg/ml;吸收相半衰期(t1/2k_a)为0.342h,消除相半衰期(t1/2k_e)为1.165h;表观分布容积(Vd)为0.88L/kg;体清除率(BIC)为0.25L/kg/h。咪唑苯脲在牛的肝、肾、心,胆汁、脑、肌肉、脂肪中的残留量:停药后1个月分别为0.94、1.47、1.10、1.89,0.81、1.47和0.72μg/g;停药后2个月分别为0.763、0.454、0.232、0.493、0.106、0.662和0.441μg/g;停药后3个月分别为0.512、0.326、0.174、0.019、0.067、0.183和0.058μg/g。     

加米霉素在比格犬体内的药代动力学研究

为探究加米霉素在比格犬体内的药物代谢动力学特征,了解其在比格犬机体内的吸收、分布、转化以及排泄规律,选取6只比格犬,加米霉素以推荐剂量6 mg/kg皮下以及静脉分别单次给药,分别于不同时间点静脉采集犬血液,用高效液相色谱串联二级质谱法测定血液中药物浓度。用非房室模型对药时曲线进行分析,皮下注射药动学参数为:达峰时间(T_(max))为0.875 h±0.186 h,消除半衰期(T_(1/2β))为59.978 h±7.861 h,药时曲线下面积(AUC)为4.912μg·h/mL±0.738μg·h/mL。静脉注射药动学参数为:达峰时间(T_(max))为0.336 h±0.144 h,消除半衰期为(T_(1/2β))为49.028 h±5.012 h,药时曲线下面积(AUC)为3.774μg·h/mL±0.211μg·h/mL。试验结果表明,静脉或皮下注射加米霉素后,药物在比格犬体内的浓度较高,且皮下注射的生物利用度较高,推荐使用皮下注射的方式给药。     

5种土霉素注射液在山羊体内的药动学比较

为了研究5种土霉素注射液肌肉注射后在山羊体内的药动学特征,给临床用药及其研究提供参考依据,选取30只山羊为靶动物,将其随机分为5组,分别注射不同品种的土霉素注射液(10%A、B、C)和(20%D、E),然后采用高效液相色谱法对山羊体内的土霉素含量进行测定,3P97软件拟合血药浓度-时间曲线,计算药动学参数。结果显示,5种土霉素注射液均符合一级吸收二室模型,10%A、10%B、10%C、20%D和20%E主要药动学参数分别为:消除半衰期(t_(1/2β))为7.13μg/mL、6.62μg/mL、6.97μg/mL、21.16μg/mL和27.32μg/mL;达峰浓度(C_(max))为(2.71±0.37)μg/mL、(3.11±0.81)μg/mL、(3.60±0.83)μg/mL、(5.52±0.53)μg/mL和(4.69±1.20)μg/mL;达峰时间(T_(max))为(2.08±1.52) h、(2.17±2.2) h、(3.05±2.30) h、(2.05±0.80) h和(2.80±1.01) h;药时曲线下面积(AUC)为(61.41±20.94) h·μg/mL、(50.34±8.74) h·μg/mL、(58.57±7.31) h·μg/mL、(124.23±7.23) h·μg/mL和(109.47±22.35) h·μg/mL。表明高浓度(20%)的土霉素注射液具有半衰期长,峰浓度高,药时曲线下面积大等特点,与低浓度(10%)土霉素注射液之间差异显著,可能与有机溶媒的用量和种类有关,此结论为临床合理使用剂型提供依据和指导。     

恩诺沙星及其代谢物在1日龄鸡体内的药动学研究

研究不同剂量恩诺沙星(ENR)及代谢产物环丙沙星(CIP)在雏鸡体内药动学特征。240只刚出壳黄羽肉鸡分2个剂量组,20 mg/kg和40 mg/kg皮下注射恩诺沙星,高效液相色谱法测定药物浓度,药时数据用WinNolin8.0软件处理非房室模型分析。结果表明,增加剂量后恩诺沙星以下药动参数发生变化:消除半衰期(t_(1/2))由7.37 h降至6.53 h,达峰时间(T_(max))由8 h降到4 h,最大血药浓度(C_(max))由3.75μg/mL增至4.92μg/mL,药时曲线下面积(AUC_(last))由40.45 h·μg/mL增至78.2 h·μg/mL,平均滞留时间(MRT_(last))由为8.6 h增至11.42 h;消除率(Cl)分别为0.49 L/h/kg和0.5 L/h/kg,表观分布容积(Vz_(obs))分别为5.22 L/kg和4.77 L/kg。不同剂量恩诺沙星给药后都都表现出分布迅速、广泛的特点,代谢产物环丙沙星产生与消除迅速。     

硫酸小檗碱微球制剂在绵羊体内的药代动力学研究

为研究硫酸小檗碱微球在绵羊体内的药代动力学,选取10只绵羊,随机分为2组,分别颈部皮下注射2%硫酸小檗碱微球制剂和2%硫酸小檗碱水溶液,在不同时间点颈静脉采血,经前处理后利用高效液相色谱进行含量检测。通过DAS2.1.1软件进行数据统计分析,结果显示硫酸小檗碱微球组达峰时间T_(max)为8 h,消除半衰期T_(1/2Z)为5.22 h,达峰浓度C_(max)为0.31μg/mL,清除率C_(Lz/F)为0.46 L/(kg·h);而硫酸小檗碱水溶液组达峰时间T_(max)为1 h,消除半衰期T_(1/2Z)为2.35 h,达峰浓度C_(max)为0.28μg/mL,清除率C_(Lz/F)为2.21 L/(kg·h)。结果表明,硫酸小檗碱微球制剂与硫酸小檗碱水溶液相比具有更迟的达峰时间(P0.05),更长的消除半衰期(P0.05),在体内可起到缓释的效果。     

氟苯尼考环糊精包合物的药物代谢动力学研究

为研究氟苯尼考环糊精包合物的药代动力学及生物利用度,将健康白羽肉鸡24只,随机分为两组,每组12只,分别以20 mg/kg的剂量单次灌服20%普通氟苯尼考粉(A组)和20%氟苯尼考环糊精包合物(B组),并于给药后不同时间点从翅下静脉采血,采用已建立的UPLC-MS/MS测定血浆中的药物浓度,用WinNonlin 5.2.1药动学分析软件的非房室模型拟合血药浓度-时间数据。结果显示:A组达峰时间(T_(max))和达峰浓度(C_(max))分别为1.563±0.755 h、1043.15±391.42 ng/mL,平均消除半衰期(T_(1/2λz))约为4.814±3.058 h,平均曲线下面积(AUC_(last))为4283.53±2406.81 h·ng/mL;B组T_(max)、C_(max)分别为1.417±1.683 h、4691.95±1597.28 ng/mL,T_(1/2λz)约为2.106±1.476 h,AUC_(last)为14911.70±2976.22 h·ng/mL;相对生物利用度约为348.12%。试验表明,采用环糊精包合工艺的氟苯尼考粉的生物利用度显著高于普通工艺的氟苯尼考粉。     

双氯芬酸钠注射液在猪体内的药物动力学和生物利用度研究

研究双氯芬酸钠注射液在猪体内的药物动力学特征和生物利用度,为其临床合理使用提供实验依据。选用8头健康猪,采用两周期随机交叉实验设计,单剂量静脉注射或肌内注射5%双氯芬酸钠注射液(2.5mg·kg~(-1)),高效液相色谱法(HPLC)检测猪血浆中双氯芬酸钠浓度,采用DAS 2.1.1软件对血药浓度-时间数据进行非房室模型分析,计算药动学参数。结果显示,猪静脉注射给药的药动学参数如下:消除半衰期(T_(1/2β))为(1.32±0.34)h,药-时曲线下面积(AUC)为(55.50±5.50)(μg·mL~(-1))·h,平均滞留时间(MRT)为(1.60±0.28)h,表观分布容积(V_d)为(0.50±0.05)L·kg~(-1),总体清除率(CL_B)为(0.26±0.04)L·(h·kg)-1。猪肌内注射给药的药动学参数如下:峰时(T_(max))为(1.19±0.26)h,峰浓度(C_(max))为(11.61±5.99)μg·mL~(-1),T_(1/2β)为(1.87±0.70)h,AUC为(43.17±7.77)(μg·mL~(-1))·h,MRT为(2.86±0.64)h,生物利用度(F)为(78.29±14.81)%。结果提示,双氯芬酸钠注射液肌注给药后在猪体内具有吸收良好、达峰迅速、血药峰浓度高、消除较快、生物利用度较高的药物动力学特征,临床推荐给药剂量为2.5mg·kg~(-1)。     

伊维菌素微乳剂在绵羊体内的药代动力学研究

研究伊维菌素微乳剂在绵羊体内的药代动力学,对比高含量伊维菌素微乳剂与普通注射剂型的生物利用度差异。选取12只绵羊,分为2组,按照0.2 mg/kg体重分别皮下注射10 mg/mL伊维菌素注射液和30 mg/mL伊维菌素微乳剂。分别在给药前0.5 h,给药后2、4、6、8、10、12、16、20、24、36、48、96、144、192、240、336 h在颈静脉采集血液备用,用高效液相色谱荧光检测器对绵羊血浆中的伊维菌素进行检测,并利用内标法计算其含量。通过DAS2.1.1软件进行数据统计分析。结果显示,伊维菌素微乳剂组药时曲线下面积(AUC)为3 812.17 ng/mL·h,达峰浓度(C_(max))为97.71 ng/mL,达峰时间(T_(max))为12 h,消除半衰期(T_(1/2z))为43.46 h;伊维菌素注射液组AUC为2 501.25 ng/mL·h,C_(max)为48.15 ng/mL,T_(max)为24 h,T_(1/2z)为44.96 h。说明伊维菌素微乳剂吸收效果好,达峰时间短,达峰浓度高,生物利用度高。     

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。     

两种氟苯尼考粉剂在肉鸡体内的药动学比较

健康黄羽肉鸡(公母各半)20只随机分为A、B 2组,分别单剂量灌服19.91%氟苯尼考粉(受试品)和10%氟苯尼考粉(对照品),给药量均为15 mg/kg,进行药动学比较研究。给药后按预定时间采集血样,采用高效液相色谱法(HPLC)法测定血浆中药物含量。实测血药浓度-时间数据,采用Win Nonlin 5.2.1药动学分析软件处理。结果显示:A组平均消除半衰期(T_(1/2β))约为9.158 h,达峰时间(T~(max))和峰值浓度(C~(max))分别为0.600 h和5.786μg/m L,平均曲线下面积(AUC)为26.474 h·μg/m L,平均滞留时间(MRT)4.357 h;B组平均T_(1/2β)约为7.513 h,T~(max)和C~(max)分别为1.900 h和5.106 mg/L,AUC为25.749 h·μg/m L,MRT 5.695 h;相对生物利用度约为93.979%。结果表明,19.91%氟苯尼考粉T~(max)比10%氟苯尼考粉提前(P0.01),其他药动学参数无明显差异(P0.05)。     

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.     

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.     

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.     

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

Tropical Animal Health and Production -     

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.     

Chemotaxis of macrophage in inflammation

Our particular attention in this article was given to natural mediators for macrophages isolated from the sites of tissue injury. A number of chemotactic factors, which may satisfy many criteria making them acceptable as inflammatory leucocyte chemotactic factors, has been separated. Among them, our laboratory has isolated three macrophage (monocyte) chemotactic factors (MCF-a, -b and -c). Their purification, characterization and functional specificity are discussed.     

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