Pharmacokinetics and Pharmacodynamics of a Depolymerized Glycosaminoglycan from Holothuria fuscopunctata,a Novel Anticoagulant Candidate,in Rats by Bioanalytical Methods

dHG-5 (Mw 5.3 kD) is a depolymerized glycosaminoglycan from sea cucumber Holothuria fuscopunctata. As a selective inhibitor of intrinsic Xase (iXase), preclinical study showed it was a promising anticoagulant candidate without obvious bleeding risk. In this work, two bioanalytical methods based on the anti-iXase and activated partial thromboplastin time (APTT) prolongation activities were established and validated to determine dHG-5 concentrations in plasma and urine samples. After single subcutaneous administration of dHG-5 at 5, 9, and 16.2 mg/kg to rats, the time to peak concentration (T_max) was at about 1 h, and the peak concentration (C_max) was 2.70, 6.50, and 10.11 μg/mL, respectively. The plasma elimination half-life(T_1/2β) was also about 1 h and dHG-5 could be almost completely absorbed after s.c. administration. Additionally, the pharmacodynamics of dHG-5 was positively correlated with its pharmacokinetics, as determined by rat plasma APTT and anti-iXase method, respectively. dHG-5 was mainly excreted by urine as the unchanged parent drug and about 60% was excreted within 48 h. The results suggested that dHG-5 could be almost completely absorbed after subcutaneous injection and the pharmacokinetics of dHG-5 are predictable. Studying pharmacokinetics of dHG-5 could provide valuable information for future clinical studies.     

金莲花植物成分及其药剂的研究进展

综述了金莲花的植物学及植物化学、成分分析、药理作用、临床应用及制剂等方面的研究状况，并对目前研究存在的问题及以后的发展前景进行了讨论。     

盐酸吡利霉素治疗奶牛乳房炎临床药效学及对乳品质影响的研究

本研究依据对黑龙江省部分牧场奶牛乳房炎致病菌分离鉴定以及药敏试验结果,选取盐酸吡利霉素、头孢噻呋钠和复方阿莫西林为试验药物,对患有隐性乳房炎的奶牛进行治疗并对乳品质进行跟踪监测。结果表明盐酸吡利霉素对隐性乳房炎的治愈率最高,对临床型乳房炎的治疗效果略差于复方阿莫西林,盐酸吡利雷素与复方阿莫西林对两种类型乳房炎治疗的总有效率相当,但盐酸吡利霉素对乳品质（尤其是降低体细胞数方面）的改善作用显著好于复方阿莫西林治疗组。     

氟苯尼考在鲫和草鱼体内的药代/药效动力学联合参数及其临床给药方案的研究

为研究氟苯尼考在鲫和草鱼体内的药代学、药效动力学联合参数,并制定氟苯尼考对鲫、草鱼的精确用药方案,本实验结合氟苯尼考对致病性嗜水气单胞菌CAAh01的体外药效学研究和口灌不同剂量的氟苯尼考在鲫、草鱼体内药代动力学研究,确定了氟苯尼考防治该致病菌引起的鲫和草鱼细菌性败血症的给药方案。研究结果显示,氟苯尼考对CAAh01菌株的最小抑菌浓度(MIC)为0.5μg/mL,最小杀菌浓度(MBC)为1.0μg/mL,防细菌耐药突变浓度(MPC)为6.0μg/mL,防耐药突变选择窗(MSW)为0.5~6.0μg/mL。按10、20、30 mg/kg体质量剂量对鲫、草鱼口灌氟苯尼考后,在鲫体内,血药浓度大于MPC的维持时间分别为5、8、24 h;AUC24/MIC分别为177.06、265.90、426.50;Cmax/MIC分别为15.59、21.32、31.24。在草鱼体内,血药浓度大于MPC的维持时间分别为0、0、3 h;AUC24/MIC分别为38.60、75.08、121.94;Cmax/MIC分别为4.75、10.08、19.99。研究表明,综合血药浓度维持MPC以上的时间、AUC24/MIC或Cmax/MIC指标,氟苯尼考适用于鲫细菌性疾病的防治,其防突变用药方案为剂量30 mg/kg,每日1次给药,休药期不低于20 d。对于草鱼细菌性疾病的防治,氟苯尼考不宜连续使用。     

几种杀菌剂对南方红豆杉炭疽病的田间药效测定

在田间药效测定中,喷雾和注干两种施药方法相比,喷雾防治的效果明显好于注干的防治效果。喷雾试验中,防治效果最好的是甲基托布津,平均防治效果达到78.79%,最差的是退菌特,平均防治效果为57.20%;在注干防治试验中,防治效果最好的依然为甲基托布津,为62.50%,其次为炭克、多菌灵,最差的为退菌特,为46.57%。     

治疗多重耐药革兰氏阴性菌感染的有效抗菌药——多黏菌素

综述了多黏菌素的理化性质、抗菌活性、药动学、药效学、临床应用、残留等方面的特点和研究概况,以期为该药在兽医临床上的应用提供依据。     

氨基糖苷类药物抗生素后效应的研究进展

对氨基糖苷类药物抗生素后效应的产生机制、体内外的研究方法、影响因素及常用氨基糖苷类药物抗生素后效应的研究现状进行概述,为评价氨基糖苷类药物的药效学指标和在兽医临床的合理应用提供理论基础。     

新一代驱虫抗生素—莫西菌素

莫西菌素同伊维菌素一样 ,是一种目前广泛用于兽医临床的广谱、高效、新型大环内酯类驱虫抗生素 ,是美贝霉素家族中的一员。由于其独特的理化性质 ,在国外 ,已被广泛用于治疗奶牛、猪等动物体内外寄生虫病。文章对莫西菌素的理化特性、作用机制、药动学、制剂、药效、耐药性、毒性、残留等进行了较详细地综述 ,同时也介绍了减少耐药性产生的一些方法 ,为该药能在国内应用提供第一手资料 ,以求为兽医临床用药提供参考     

Amoxicillin—current use in swine medicine

Amoxicillin has become a major antimicrobial substance in pig medicine for the treatment and control of severe, systemic infections such as Streptococcus suis. The minimum inhibitory concentration 90% (MIC 90) is 0.06 μg amoxicillin/ml, and the proposed epidemiological cut‐off value (ECOFF) is 0.5 μg/ml, giving only 0.7% of isolates above the ECOFF or of reduced susceptibility. Clinical breakpoints have not been set for amoxicillin against porcine pathogens yet, hence the use of ECOFFs. It has also been successfully used for bacterial respiratory infections caused by Actinobacillus pleuropneumoniae and Pasteurella multocida. The ECOFF for amoxicillin against A. pleuropneumoniae is also 0.5 μg/ml demonstrating only a reduced susceptibility in 11.3% of isolates. Similarly, P. multocida had an ECOFF of 1.0 μg/ml and a reduced susceptibility in only 2.6% of isolates. This reduced susceptibility disappears when combined with the beta‐lactamase inhibitor, clavulanic acid, demonstrating that it is primarily associated with beta‐lactamase production. In contrast, amoxicillin is active against Escherichia coli and Salmonella species but using ECOFFs of 8.0 and 4.0 μg/ml, respectively, reduced susceptibility can be seen in 70.9% and 67.7% of isolates. These high levels of reduced susceptibility are primarily due to beta‐lactamase production also, and most of this resistance can be overcome by the combination of amoxicillin with clavulanic acid. Currently, amoxicillin alone is considered an extremely valuable antimicrobial in both human and animal medicine and remains in the critically important category of antibiotics alongside the fluoroquinolones and macrolides by the World Health Organization as well as the third‐ and fourth‐generation cephalosporins, but these cephalosporins show marked resistance to basic beta‐lactamase production and are only destroyed by the extended‐spectrum beta‐lactamases. Amoxicillin alone and in combination with clavulanic acid are currently classed together in Category 2 in the European Union. By reviewing the pharmacodynamic data and comparing this with pharmacokinetic data from healthy and infected animals and clinical trial data, it can be seen that the product has a good efficacy against S. suis and A. pleuropneumoniae, in spite of usage over many years. However, it may be much less efficacious on its own against E. coli, due to reduced susceptibility and resistance associated with beta‐lactamase production, which is largely overcome by the use of clavulanic acid. It is felt that this differentiation may be useful in future classification of amoxicillin alone, in comparison with its combined use with clavulanic acid and thereby preserve the use of the more critically important antibiotics in veterinary medicine and reducing the risk of their resistance being transmitted to human.     

藏草乌水煎提取液体外杀灭羊虱蝇药效及皮肤毒性试验研究

试验旨在研究藏草乌的水煎提取液在体外杀灭羊虱蝇的药效作用及其皮肤毒性、刺激性、过敏性试验,为藏草乌的开发利用和临床应用提供理论依据。将1%、2%、4%、8%、10%藏草乌水煎提取液分别滴于衬有吸水纸和羊虱蝇的平皿中,在1、2、4、8 h时分别观察其对羊虱蝇的杀灭情况。取相同剂量1%、2%藏草乌水煎提取液均匀涂于大白兔的完整皮肤和破损皮肤,进行皮肤毒性、刺激性和过敏性试验。结果显示,给药1 h后各浓度的藏草乌水煎提取液及阳性对照组均出现了不同程度的羊虱蝇杀灭效果,4 h后阳性对照组杀灭率为100%,8 h时,1%、2%藏草乌水煎提取液杀灭率达到70%,而2%藏草乌水煎提取液较1%药物组杀灭羊虱蝇效果好;皮肤毒性试验显示,大白兔皮肤无红斑、水肿,体重变化正常;皮肤刺激性试验结果显示,藏草乌提取液对大白兔皮肤无刺激性;皮肤致敏反应结果表明,藏草乌提取液对大白兔不具有致敏性。综上所述,藏草乌水煎提取液具有良好的体外杀灭羊虱蝇作用,且皮肤用药安全。