家兔大椎穴注射扑热息痛的药动学研究

目的:研究扑热息痛注射液于家兔大椎穴注射后的药动学特征。方法:健康家兔8只,扑热息痛单剂量(20mg/kg)于大椎穴注射后,在规定时间点采血,HPLC检测血药浓度,DAS药动学软件处理药时数据。结果:药时数据符合一级吸收二室模型(权重=1/C2),主要药动学参数为:Cmax=23.1880±2.4785(mg/l),tpeak=0.5000±0.0000(h),t1/2Ka=0.3821±0.1086(h),t1/2α=2.1260±0.9838(h),t1/2β=10.1621±4.0967,AUC(0-12h)=34.5331±4.181(mg/l.h),Ka=3.7364±1.2723(h),MRT(0-12h)=1.3159±0.0581(h)。结论:扑热息痛于家兔大椎穴注射后,药物迅速达到峰值,血药浓度高,有效血药浓度维持时间长,药物体内分布广泛。     

复方黄柏颗粒剂在小鼠体内的药代动力学

为探讨复方黄柏颗粒剂有效成分-盐酸小檗碱在小鼠体内的药动学特征,按25 g/kg(相当于盐酸小檗碱10.95 mg/kg)的剂量经口给予小鼠复方黄柏颗粒剂,用高效液相色谱法检测用药后不同时间血浆中盐酸小檗碱的质量浓度,研究在小白鼠体内的药物动力学。结果表明口服复方黄柏颗粒的有效成分-盐酸小檗碱在小鼠体内的药时数据符合开放性二室模型,动力学方程为C=17.8e-0.859 81t 14.51e-0.636 1t。主要药代动力学参数:t1/2α为(0.81±0.07)h,t1/2β为(5.25±2.96)h,t1/2Ka为(0.76±0.05)h,AUC0→∞为(3.389 3±0.437 4)mg.L-1.h,CL/F为(3.281 8±0.446 3)L/h,Vd/F为(13.65±22.38)L/kg,Tpeak为(1.617 19±0.056 50)h,Cmax为(1.149 98±0.056 04)μg/mL。     

三苯双脒肠溶片在羊体内药物代谢动力学试验

为研究三苯双脒在绵羊体内动态变化的规律,采用方法如下:绵羊1次口服给药60、120、180 mg/kg体重3个剂量组,依据消除速率常数、吸收率常数、达峰时、血药浓度-时间曲线等主要药动学参数,经上海宏能软件有限公司开发的临床药物代谢动力学软件进行数据分析,符合血管外给药一级吸收一室模型,主要药动学参数为:吸收率常数Ka=0.15129h,t1/2Ka=4.74h,消除速率常数Ke=0.082 121h,t1/2Ke=8.46h,t1/2=19.03 h,达峰时tmax=8.0 h,Cmax=6257μg/L,血药浓度-时间曲线下面积AUC=300 51μg/L.h。三苯双脒肠溶片在羊体内吸收快、半衰期长等特点。说明三苯双脒肠溶片在药效试验剂量范围内比较安全。     

中药复方中葛根素在肉鸽体内的代谢特征研究

运用高效液相色谱法测定分析了中药复方(葛银方剂)中葛根素在肉鸽体内的代谢情况,以120mg/只灌胃后通过药动学参数变化来评价药的相互作用。测定血药浓度,并用3P87程序拟合药动学参数。结果发现,单味煎剂和中药复方灌服后15min血浆中即可检出葛根素,在15～4h才会出现药浓度最高峰。葛根素在肉鸽体内呈二室模型分布,单味煎剂中葛根素主要药动学参数为t1/2α=1422022h,t1/2β=7862796h,Cmax=0732025μg/L,Tpeak=1818334h;中药复方中葛根素主要药动学参数是t1/2α=2128758h,t1/2β=5108140h,Cmax=1037176μg/L,Tpeak=1383717h。结果表明,中药复方中葛根素在肉鸽体内的代谢具有速度快、吸收强的特点。     

黄连解毒散超微细粉中黄芩苷在家兔体内的药代动力学研究

采用高效液相色谱法测定灌胃给予黄连解毒散超微细粉和细粉的家兔血浆中黄芩苷的浓度,血药浓度-时间数据经药代动力学分析软件(Pharmaceutical Kinetics Software,PKS)处理,比较黄连解毒散超微细粉和普通细粉中黄芩苷在家兔体内的药代动力学参数。结果如下:黄连解毒散超微细粉组、普通细粉组黄芩苷的药代动力学最佳模型均为二室开放模型。黄连解毒散超微细粉主要药动学参数:Ka=0.497 h-1,t1/2α=2.556 h,t1/2β=8.46 h,AUC0→∞=3.401μg.h/mL,Vd=6.752 L/kg,Tpeak=3.005 h,Cmax=0.311μg/mL;黄连解毒散普通细粉主要药动学参数:Ka=0.419 h-1,t1/2α=2.74 h,t1/2β=5.83 h,AUC0→∞=2.611μg.h/mL,Vd=12.890 L/kg,Tpeak=3.645 h,Cmax=0.215μg/mL。与细粉比较,黄连解毒散超微细粉中黄芩苷的相对生物利用度提高了30.26%。上述结果表明,黄连解毒散经超微粉碎后吸收相增大,可显著提高其有效成分黄芩苷的生物利用度。     

阿维菌素微囊在家兔体内的药动学研究

为了考察阿维菌素微囊在家免体内的药动学行为,将10只家兔随机分为2组,皮下注射阿维菌素微囊注射液（1．0mg／kg）和普通阿维菌素注射液（0．2mg／kg）,用高效液湘色谱法测定家兔血浆中阿维菌素的浓度,3P87药动学软件处理血浆药物浓度-时间数据。研究结果表明,阿维菌素微囊注射液和普通阿维菌素注射液药-时数据都符合一级吸收二室开放模型,阿维菌素微囊注射液的主要动力学参数分别是t1/2kα=21．72h;t1/2α=56．65h;t1／2β=239．43h;tmax=63．05h;Cmax=34．30ng／mL;AUC=11573．88ng／mL·h。普通阿维菌素注射液的主要动力学参数分别是t1/2kα=7．38h;t1/2α=14．59h;t1／2β=32．84h;tmax=19．78h;Cmax=20．88ng／mL;AUC=1482．04ng／mL·h。说明阿维菌素微囊化后。与普通阿维菌素注射泣相比,吸收慢,消除慢,作用时间长．生物利用度显著提高。     

盐酸诺氟沙星在家蚕体内的药物动力学研究

为了给家蚕细菌病的预防和治疗提供合理用药的理论依据 ,采用微生物测定法研究了盐酸诺氟沙星在健康家蚕体内的药物动力学特征 ,以MCPKP药代动力学程序处理药时数据。结果表明 :盐酸诺氟沙星在蚕体内的药时数据符合一级吸收一室开放式模型 ,主要药物动力学参数 :T1/2Ka=1 797± 0 0 2 3h ,T1/2Kel=1 778± 0 0 12h ,Tmax=3 4 2 8± 0 0 0 8h ,Cmax=14 80 8± 0 6 4 5 μg/mL。     

磺胺嘧啶在实验性肾功能损害家兔体内的药代动力学研究

分别测定了SD在6只健康家兔及6只肾损害家兔体内的代谢动力学参数。单剂量静脉快速注射SD 140mg／kg，8h内不同时间心脏采血，测定血药浓度。结果表明，SD在家兔体内的药代动力学配置符合无吸收因素二室开放模型。药-时曲线方程为：C正常=13．429e^-7.968t和 32．928e^-0.522t，C肾损=16．559e^-3.942t 26．433e^-0.322t。肾损害家兔与健康家兔相比，α下降了50．53％；8下降了38．34％；t1／2α延长了123．46％；t1／2β延长了63．15%；AUC增加了34．22％；CLB降低了22．12％。结果显示家兔肾功能损害后，SD在其体内代谢发生了显著变化。提示在肾脏损害时应相应增大SD给药间隔时间或减小给药剂量。     

盐酸多西环素在猪体内的药物动力学及其残留

试验建立了反相高效液相色谱(RT-HPLC)法测定盐酸多西环素的浓度,探讨了盐酸多西环素在猪体内的药物动力学和残留特征。结果表明,盐酸多西环素以2.5mg/kg单剂量肌内注射给猪(n=6),药物动力学模型符合有吸收一室模型,药物动力学参数:吸收半衰期(t1/2ka)、消除半衰期(t1/2ke)为(0.400±0.312)h、(9.530±0.956)h,药时曲线下面积(AUC)为(44.414±4.123)mg·h·L-1,最大血药浓度(Cmax)为(2.811±0.136)mg/L,达峰时间(Tp)为(1.910±0.213)h。另外,以相同剂量肌内注射给猪(n=6),每天1次,连续给药4d后,在不同时间测定盐酸多西环素在猪的肌肉、肝脏、肾脏、皮肤和脂肪中的残留量。在给药后16d,盐酸多西环素在各组织均能检测到,且残留均低于残留限量。盐酸多西环素注射液在猪体内消除缓慢,残留期较长,建议休药期不低于16d。     

盐酸沙拉沙星在蛋鸡体内的血液动力学的研究

为研究盐酸沙拉沙星在蛋鸡体内血液动力学 ,选用成年健康蛋鸡 6 5只进行试验。按 10mg/kg体重口服给药后 ,测定血清中盐酸沙拉沙星的含量。结果表明 :盐酸沙拉沙星在血液中经时过程符合一级吸收一室模型 ,其理论方程为Cb=1.0 36 (e-0 .173 5t-e-2 .0 57t)。Ka 为 1.6 0 2 5h-1、Cmax为 0 .74 2 9μg/mL、tmax为 1.5 80 7h。由抗生素后效应及药动学参数 ,建议临床给药口服方案为 10 .12mg/kg。     

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.     

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