丙泊酚注射液对靶动物犬的安全性评价

为研究丙泊酚注射液对靶动物犬的安全性,选取健康成年贵宾犬32只,随机分为4组,每组8只,各组试验犬分别按0、1倍推荐剂量(5.5 mg/kg·bw)、3倍推荐剂量(16.5 mg/kg·bw)、5倍推荐剂量(27.5 mg/kg·bw)单剂量静脉注射丙泊酚注射液,并对各组试验犬进行临床观察及各项生理指标检查。结果显示,各组试验犬血液学及血液生化指标变化均在正常范围内,苏醒后各组试验犬生理指标与空白对照组差异不显著,5倍推荐剂量组与空白对照组试验犬各脏器均未观察到异常病理变化。除3倍和5倍推荐剂量组部分试验犬出现呼吸抑制外,各剂量组试验犬均未出现死亡等其他不良反应。试验表明,丙泊酚注射液按推荐剂量给药对靶动物犬是安全的。     

蜘蛛香胶囊对靶动物犬的安全性试验

为了评价蜘蛛香胶囊对靶动物犬的安全性,试验选择24只试验犬,随机分为3组,分别为1倍推荐剂量(50 mg/kg)组、3倍推荐剂量(150 mg/kg)组和5倍推荐剂量(250 mg/kg)组,每天口服给药2次,连续给药3 d。分别在给药前1天、给药后第1天、第3天、第5天采集血液,对犬的血常规和血液生化指标进行分析比较,并观察给药前后犬的临床症状变化。结果表明:试验期间各剂量组犬临床症状正常,给药后的血常规和血液生化指标与给药前相比无显著差异(P0.05)。说明蜘蛛香胶囊在5倍推荐剂量(250 mg/kg)范围内连续给药3 d,对靶动物犬的临床体征和血液生理生化指标无明显影响,该药临床应用安全。     

酮洛芬注射液对靶动物奶牛的安全性研究

为研究酮洛芬注射液对靶动物奶牛的安全性,选择20头健康泌乳奶牛,随机分成4组,即1倍(3 mg/kg·bw)、3倍(9 mg/kg·bw)、5倍(15 mg/kg·bw)推荐剂量组和空白对照组(生理盐水)。采用肌肉注射给药每日1次,连续给药9 d,观察用药后奶牛的健康状况、直肠温度等临床症状,并进行血常规、血清生化指标的测定。结果显示,使用推荐剂量(3 mg/kg·bw)至5倍推荐剂量(15 mg/kg·bw)的酮洛芬注射液,整个试验期间受试牛临床观察未发现明显的不良反应,血常规、血清生化指标检测结果均在正常范围内,表明酮洛芬注射液在临床上用于靶动物奶牛是安全的。     

加米霉素注射液在靶动物猪的安全性试验

为评价加米霉素注射液对靶动物猪的安全性,将24头70日龄大长二元杂交猪随机分为4组,每组6头,分别为空白对照组(生理盐水)、1倍推荐剂量组(6 mg/kg·bw)、3倍推荐剂量组(18 mg/kg·bw)、5倍推荐剂量组(30 mg/kg·bw),分别于试验第0天、5天、10天各肌肉注射给药一次。通过观察猪的临床表现、增重情况,测定其血液常规指标、血液生化指标,观察组织病理变化等评价加米霉素注射液的安全性。试验结果显示,加米霉素注射液1倍、3倍、5倍推荐剂量组的各项指标与空白对照组相比无显著性差异(P 0. 05)。试验结果表明,加米霉素注射液以5倍推荐剂量给药对靶动物猪安全。     

美洛昔康片剂在比格犬内的药代动力学及生物利用度研究

本研究以0.1 mg/kg体重的剂量研究美洛昔康片在比格犬中的药代动力学和生物利用度。HPLC分析血浆中的药物浓度,WinNonlin 6.4非房室模型计算药动学参数。比格犬内服美洛昔康片后测得0~48 h美洛昔康的T1/2、Cmax、Tmax和AUC0-t分别为14.55 ± 2.18 h、296.16 ± 74.15 ng·mL-1、6.0 ± 0.00 h和6356.79 ± 1089.78 ng·h·mL-1;比格犬静脉注射美洛昔康溶液后,测得0~48 h美洛昔康的T1/2和AUC0-t分别为11.54 ± 4.18 h和5510.68 ± 1075.29 ng·h·mL-1。内服美洛昔康片剂的绝对生物利用度为115.35%。美洛昔康片在比格犬体内消除速率较慢,消除半衰期较长,在体内滞留时间较长,绝对生物利用度高,药物在体内作用时间较长等药动学特征。     

癸氧喹酯溶液对靶动物鸡的安全性试验

为了评价癸氧喹酯溶液对靶动物鸡的安全性,选取100只健康的8日龄扬州AA肉鸡,随机分成5组,每组20只。各组试验鸡分别以0、推荐剂量(15 mg/kg)、3倍推荐剂量(45 mg/kg)、5倍推荐剂量(75 mg/kg)、10倍推荐剂量(150 mg/kg)的癸氧喹酯溶液连续饮水给药21 d,通过对一般临床症状、增重、饲料报酬、血液学和血液生化指标、病理组织学等观察和检测,结果表明:癸氧喹酯溶液毒性较小,在鸡体内耐受性高,至少以5倍推荐剂量饮水给药对靶动物鸡是安全的。     

美洛昔康注射液对犬髋关节发育不良的镇痛作用研究

为考察美洛昔康注射液的镇痛效果,本试验选择自然发病的髋关节发育不良犬,用美洛昔康注射液和阳性对照药替泊沙林片进行相应的治疗,观察其临床疗效。选择步态、爬高、针刺腹部皮肤痛感作为主要评价指标,以体温、呼吸频率、心率和采食率为辅助指标,评价其疗效和安全性。结果表明,试验药物组犬的运步评分与对照组无明显差异;爬高评分在用药后第2天两组即有所升高,第5天试验药物组显著高于对照组;针刺腹部皮肤痛感评分在用药后第4、5天两组的数值无显著差异,其他时间试验药物组低于对照组;用药后两组犬的体温(37.5~39℃)、呼吸频率(20~40次/min)和心率(80~120次/min)均在正常范围内,采食率变化轻微。皮下注射美洛昔康注射液,首次0.2 mg/kg·bw,维持剂量0.1 mg/kg·bw,每天1次,连用7 d,可有效控制疼痛,且无明显副作用。     

加米霉素注射液的靶动物安全性试验

为了评价加米霉素注射液对靶动物牛的安全性,选择24头健康中国荷斯坦牛犊,随机分成4组,每组6头。各组分别以对照组(生理盐水:0.2 mL/kg·bw)、推荐剂量组(6 mg/kg·bw)、3倍推荐剂量组(18 mg/kg·bw)和5倍推荐剂量组(30 mg/kg·bw)的加米霉素注射液给药。试验期间观察受试牛的临床表现和体重变化,试验结束后进行组织病理学检查,测定血液学和血清生化指标的变化。结果表明,使用推荐剂量和3倍推荐剂量的加米霉素注射液,整个试验期间受试牛精神状态、饮水、采食和粪便等均未出现异常,体温、心率、呼吸频率、增重和饲料消耗量与空白对照相比均无显著性变化。由此可以说明,加米霉素注射液按照推荐剂量应用于牛具有较好的安全性。     

氟尼辛葡甲胺注射液对靶动物奶牛的安全性研究

为研究氟尼辛葡甲胺注射液对靶动物奶牛的安全性,选择20头健康泌乳奶牛,随机分成4组,即1×(2.2 mg/kg bw)、3×(6.6 mg/kg bw)、5×(11.0 mg/kg bw)推荐剂量组,空白对照组(注射无菌注射用水)。静脉注射给药每日1次,连续给药7 d,观察用药后奶牛的直肠温度、精神状态以及乳房局部症状等临床症状,并进行血液生理和血清生化指标的测定。结果显示,1×、3×推荐剂量组临床观察未发现明显的不良反应,血液生理、生化指标检测结果均在正常范围内,表明氟尼辛葡甲胺注射液在临床上用于靶动物奶牛是安全的。     

白苦败痢散对靶动物猪的安全性试验

为评价白苦败痢散对靶动物猪的安全性,选用4日龄健康三元杂交哺乳仔猪32只,随机分为4组,每组8只,按推荐的临床用药剂量设置白苦败痢散1倍剂量组(2 g/kg·bw)、3倍剂量组(6 g/kg·bw)、5倍剂量组(10 g/kg·bw)和对照组。3个用药组持续灌服给药7 d,每天1次,对照组灌服生理盐水。试验期间每天观察记录猪的精神状态、哺乳情况、粪便性状等表现,测定增重、血常规、血清生化指标、脏器指数并进行大体组织病理学观察。结果显示,按白苦败痢散推荐剂量的1、3、5倍剂量,持续灌服给药7 d,各观察组和测定指标与对照组相比均无显著性差异。说明白苦败痢散对猪是安全的。     

Safety of a benazepril and pimobendan combination tablet in adult healthy dogs

The objective of the study was to investigate the safety of a combination tablet of benazepril and pimobendan, Fortekor PLUS^®, in a randomized, blinded, parallel‐group design study in healthy adult beagle dogs. The test article, Fortekor PLUS^® tablets, was administered orally twice daily for 6 months at one, two, and four times the highest recommended dosage of 0.5 mg/kg benazepril hydrochloride/0.25 mg/kg pimobendan (four males and four females per group). An additional control group was sham‐dosed. Fortekor PLUS^® did not induce any treatment‐related effects on body weight, food consumption, neurological, ophthalmologic or physical assessments over the 6‐month treatment period. The test article was possibly associated with an increased frequency of occasional vomiting. Fortekor PLUS^® was associated with small, but significant, increases in heart rate and reductions in PR and QT intervals, which were assessed by electrocardiography. These effects were most probably related to reflex tachycardia secondary to reduced systemic blood pressure. Statistically significant changes in some clinical pathology variables were noted after test article administration, but were considered to be of no clinical relevance as values remained within reference ranges and/or were not dose‐dependent. No treatment‐related macroscopic or microscopic findings were observed. In conclusion, Fortekor PLUS^® tablets were well tolerated in healthy adult dogs when administered at one, two, and four times the highest recommended dosage for 6 months.     

Evaluation of the influence of meloxicam and flunixin meglumine on the apoptosis of peripheral blood CD4+ and CD8+ T cells in calves

The aim of the study was to determine whether treatment with recommended doses of meloxicam or flunixin had an effect on the apoptosis of peripheral blood T lymphocytes in calves. The study was carried out on 4-5 months old calves (n = 24, 8 per group). Experimental animals were injected subcutaneously with a single dose of 0.5 mg x kg(-1) of meloxicam or intravenously with 3 doses of 2.2 mg x kg(-1) day(-1) of flunixin. The non-treatment animals served as control. Blood samples were taken at day 0 and at days 1, 2, 3, 5, 7 and 14 after the first NSAIDs injection. Apoptosis was determined by flow cytometry using Annexin V-PE/7-AAD staining. The kinetic analysis of apoptosis in the total lymphocyte population, as well as in the CD4+ and CD8+ subsets did not reveal significant differences in the frequency of early apoptotic cells between control and experimental groups throughout the period studied. Although, 24 h after administration of the first dose of NSAIDs, late-stage apoptosis/necrosis was significantly increased in the total lymphocyte population (the meloxicam group), as well as in the CD4+ (the meloxicam group and the flunixin group) and CD8+ (the flunixin group) subsets of T cells. However, this disturbance was transient, relatively poorly expressed and, thus, unlikely to be of clinical significance. Our results indicate that the use of meloxicam or flunixin in accordance with the recommended dosage regimen in cattle do not have a clinically significant influence on apoptosis of peripheral blood T cells.     

Evaluation of adverse effects of long-term oral administration of carprofen, etodolac, flunixin meglumine, ketoprofen, and meloxicam in dogs

OBJECTIVE: To evaluate adverse effects of long-term oral administration of carprofen, etodolac, flunixin meglumine, ketoprofen, and meloxicam in dogs. ANIMALS: 36 adult dogs. PROCEDURES: Values for CBC, urinalysis, serum biochemical urinalyses, and occult blood in feces were investigated before and 7, 30, 60, and 90 days after daily oral administration (n = 6 dogs/group) of lactose (1 mg/kg, control treatment), etodolac (15 mg/kg), meloxicam (0.1 mg/kg), carprofen (4 mg/kg), and ketoprofen (2 mg/kg for 4 days, followed by 1 mg/kg daily thereafter) or flunixin (1 mg/kg for 3 days, with 4-day intervals). Gastroscopy was performed before and after the end of treatment. RESULTS: For serum gamma-glutamyltransferase activity, values were significantly increased at day 30 in dogs treated with lactose, etodolac, and meloxicam within groups. Bleeding time was significantly increased in dogs treated with carprofen at 30 and 90 days, compared with baseline. At 7 days, bleeding time was significantly longer in dogs treated with meloxicam, ketoprofen, and flunixin, compared with control dogs. Clotting time increased significantly in all groups except those treated with etodolac. At day 90, clotting time was significantly shorter in flunixin-treated dogs, compared with lactose-treated dogs. Gastric lesions were detected in all dogs treated with etodolac, ketoprofen, and flunixin, and 1 of 6 treated with carprofen. CONCLUSIONS AND CLINICAL RELEVANCE: Carprofen induced the lowest frequency of gastrointestinal adverse effects, followed by meloxicam. Monitoring for adverse effects should be considered when nonsteroidal anti-inflammatory drugs are used to treat dogs with chronic pain.     

Comparison of vedaprofen and meloxicam in dogs with musculoskeletal pain and inflammation

In this randomised, multicentre clinical study, dogs with musculoskeletal pain and inflammation were treated with either vedaprofen or meloxicam administered orally at the recommended dose rates. Clinical examinations were carried out regularly and clinical severity scores assigned. In total, 214 cases (73 acute, 141 chronic) were evaluated. Treatment with vedaprofen and meloxicam was continued for 14 and 17 days, respectively, in the acute cases, and 38 and 39 days in the chronic cases. NSAID treatment resulted in a significant improvement in clinical scores. The overall response to treatment ('responders') at the final clinical examination was 89 per cent and 87 per cent in the acute cases and 72 per cent and 65 per cent in the chronic cases in the vedaprofen and meloxicam groups, respectively. Mild transient gastrointestinal signs were observed in both groups (11 per cent vedaprofen, 12 per cent meloxicam). Adverse effects related to NSAIDs resulted in treatment cessation in 5 per cent of the dogs in each group. Vedaprofen and meloxicam were efficacious in, and well tolerated by, most of the dogs in the study.     

Safety study of a beef-based chewable tablet formulation of ivermectin and pyrantel pamoate in growing dogs, pups, and breeding adult dogs.

To determine the safety of a new combination of ivermectin and pyrantel (as pamoate salt) in a novel beef-based chewable tablet formulation, 3 tolerance trials were conducted and included growing dogs, pups, and breeding adult dogs. Growing dogs, given the combination orally for 5 consecutive days at recommended dosages (5 mg of pyrantel/kg of body weight, 6 micrograms of ivermectin/kg) or at twice the pyrantel dosage in combination with the recommended dosage of ivermectin, had no adverse effects. The combination also was administered to 6-week-old pups at 1, 3, and 5 times the recommended dose on 3 successive days for 3 times in 1 month. Compared with age-matched controls, treatment had no effect on clinical status, growth rate, or gross or histologic features. Breeding male and female dogs given the combination at 3 times the recommended dose for extended periods had no adverse effects, and prevalence of abnormalities in the offspring was not greater than that in nonmedicated controls.     

Systemic availability of o,p'-DDD in normal dogs, fasted and fed, and in dogs with hyperadrenocorticism

The systemic availability of o,p'-DDD was studied in 12 normal dogs and seven dogs with pituitary-dependent hyperadrenocorticism (PDH). The drug was given by mouth at 50 mg kg-1 and plasma o,p'-DDD concentrations were determined by gas-liquid chromatography. First, six normal dogs were given the drug three times at intervals of one week in a Latin square pattern. Systemic drug availability was found to be very poor from intact tablets in fasted dogs, better with pure drug dissolved in maize oil given by stomach tube, and best with ground tablets mixed in oil poured on dog food. Then six normal dogs and five with PDH were given one dose of o,p'-DDD as intact tablets in dog food. Systemic drug availability was good in the normal animals and, for unknown reasons, better in dogs with PDH. The half-time of elimination was shorter in dogs with PDH than in normal ones. There was evidence of a gradual rise in plasma o,p'-DDD concentrations in seven dogs with PDH treated with 25 mg kg-1 every 12 hours for 14 or 20 days. The interaction between food and o,p'-DDD probably contributes to the variation in clinical response of dogs treated with the drug. The efficiency of therapy with o,p'-DDD should be improved considerably by administering the drug with food.     

A comparison of the analgesic effects of butorphanol with those of meloxicam after elective ovariohysterectomy in dogs

This study was designed to compare the analgesic effects of butorphanol with those of meloxicam following ovariohysterectomy. Fifteen dogs were premedicated with 0.05 mg/kg body weight (BW) of acepromazine by intramuscular (IM) injection, plus 0.2 mg/kg BW of meloxicam by subcutaneous (SC) injection. Fifteen dogs were premedicated with 0.05 mg/kg BW of Acepromazine, IM, plus 0.2 mg/kg BW of butorphanol, IM. Anesthesia was induced with thiopental, and dogs were maintained on halothane. All pain measurements were performed by 1 experienced individual, blinded to treatment. Pain scores and visual analogue scales (VAS) were performed at 2, 3, 4, 6, 8, 12, and 24 hours postpremedication. An analgesiometer was used to determine the pressure required to produce an active avoidance response to pressure applied at the incision line. Pain scores, VAS, and analgesiometer scores were analyzed by using a generalized estimating equations method. A significance level of P < 0.05 was considered significant. Animals that received meloxicam demonstrated significantly lower pain scores and VAS than did animals that received butorphanol in the first 12 hours after surgery. Results of this study suggest that meloxicam will produce better postoperative analgesia than will butorphanol. Mucosal bleeding times were performed on cooperative animals in the study group (11 butorphanol, 13 meloxicam). Bleeding times were performed prior to premedication, 6 hours following premedication, and 24 hours after premedication. The 6- and 24-hour readings were compared with baseline bleeding times by using a paired t-test with a Bonferroni correction (a significance level of P < 0.025). Bleeding times did not change significantly over time.     

Comparative efficacy of flubendazole chewable tablets and a tablet combination of febantel, pyrantel embonate and praziquantel against Trichuris vulpis in experimentally infected dogs

Fourteen of 23 dogs developing patent Trichuris vulpis infections by 120 days p.i. with 5000 embryonated eggs were allocated into three groups. One group was treated with flubendazole 220 mg chewable tablets (Flubenol) at the recommended dose regimen once daily for 3 days. The second group was given the recommended single treatment with a tablet containing 150 mg febantel, 144 mg pyrantel embonate and 50 mg praziquantel in combination (Drontal Plus). The third group remained untreated. All dogs were necropsied for worm counts 10 or 11 days after (first) treatment. No worms were recovered from the flubendazole treated dogs resulting in a significant worm count reduction of 100%. In contrast, 2 of 5 animals treated with the combination of febantel, pyrantel embonate and praziquantel remained infected; the geometric mean worm burden was reduced by 99.4% as compared to the control group but did not differ significantly from those of the controls.     

Effects of preoperative administration of meloxicam on whole blood platelet aggregation, buccal mucosal bleeding time, and haematological indices in dogs undergoing elective ovariohysterectomy

The purpose of the study was to evaluate the effect of preoperative administration of meloxicam, a non-steroidal anti-inflammatory drug used for pain control, on primary haemostasis in dogs. Twenty healthy female dogs undergoing elective ovariohysterectomy were enrolled in the study. Sixty minutes before pre-anaesthesia, a single dose of meloxicam (0.2 mg/kg) was randomly administered intravenously (IV) to 10 dogs (treatment group) while control dogs received an equivalent volume of saline solution IV. Platelet aggregation, buccal mucosa bleeding time, platelet count and haematological indices were measured at 0, 1, 6 and 24 h after administration of meloxicam. Since significant differences between groups were not observed for any of the measured parameters, preoperative administration of meloxicam may be used for pain control before elective ovariohysterectomy in healthy dogs, without compromising primary haemostasis.     

Gastric retention of enteric-coated aspirin tablets in beagle dogs

Administration of acetylsalicylic acid (ASA) in the dog may cause gastric mucosal damage. Enteric-coated tablets protect the canine stomach during oral ASA medication. A therapeutic plasma salicylate concentration can be attained using enteric-coated ASA tablets at a dose rate of 25 mg/kg body wt, administered every 8 h. Six beagle dogs were given enteric-coated ASA tablets (500 mg) orally, in a 5-day cross-over experiment on two different feeding regimens: i.e. feeding once daily (Group I) or 8 hourly (Group II). Results demonstrate that feeding regimen strongly influences the plasma salicylate concentration pattern. Subtherapeutic mean plasma salicylate concentrations were found in both groups. In Group II the standard deviation (SD) of the mean plasma salicylate concentration was larger than that of Group I. The minimal plasma salicylate concentration never reached detectable levels in Group II. In both groups large numbers of tablets were vomited. Gastric evacuation of the ASA tablets is comparable to indigestible solid particles; their removal was dependent on the interdigestive gastric motility. It is concluded that large enteric-coated ASA tablets are not suitable for therapeutic use in small dogs.