氟尼辛葡甲胺

氟尼辛葡甲胺（flunixin meglumine）是一种新型的、非甾体类动物专用的解热镇痛药物，属于烟酸类衍生物，是环氧化酶的抑制剂。由美国先灵葆雅公司于20世纪90年代开发（商品名为Banamine），现已在美国、法国、瑞士、德国、英国等许多国家广泛应用。齐鲁动物保健品有限公司独立研制并申报的氟尼辛葡甲胺已于2007年6月1日被农业部批准为国家三类新兽药。证书编号为（2007）新兽药证字23、24号。     

动物专用解热镇痛抗炎药——氟尼辛葡甲胺

1理化性质 氟尼辛葡甲胺的化学名称：2-[2-甲基-3（三氟甲基）苯基]氨基]-3吡啶羧酸复合1-脱氧-1-（甲氨基）-D-山梨醇（1：1）；分子量为491．46；熔点为137～140℃。性状为白色至类白色粉末，在水或乙醇中易溶，在氯仿中难溶。     

动物专用解热镇痛抗炎新药——氟尼辛葡甲胺

氟尼辛葡甲胺（flunixin meglumine）是一种有效的非麻醉、非类固醇类的止痛剂，最早由Doran；Henry等人于1996年研制生产，美国先灵葆雅公司将其做成注射液（商品名为Baaamine），用于动物疾病的治疗。由于其疗效好、毒性低．在欧美等国家应用广泛，并于2004年10月被FDA批准用于产乳期奶牛，目前，该药在我国兽医临床应用较少．故对该药做一介绍。     

氟尼辛葡甲胺对大鼠小鼠的抗炎镇痛作用研究

氟尼辛葡甲铵盐是一种动物专用的非甾体抗炎药,具有镇痛和解热功能,但抗炎是其主要功效。本试验通过对鸡蛋清诱导的大鼠踝关节炎性肿胀模型和冰醋酸所致小鼠疼痛扭体反应来研究其抗炎镇痛效果。与对照组相比,FM高中低各剂量组(0.55、1.1、2.2 m g/kg)对大鼠足关节炎症均有显著的对抗作用(P<0.05,P<0.01),呈明显的量效关系。高剂量组(2.2m g/kg)抗炎功效明显优于吲哚美辛组(2.25 m g/kg)和地塞米松组(2.52 m g/kg)。中剂量组(1.1 m g/kg)作用堪比吲哚美辛,而低剂量组(0.55 m g/kg)稍逊于地塞米松。与同类对照药双氯芳酸钠(16.25 m g/kg)和安乃近(32.5 m g/kg)相比,结果显示FM(2.5 m g/kg)对小鼠扭体抑制作用最强,抑制率高达82.69%。     

氟尼辛葡甲胺对患呼吸道疾病奶牛的解热效果

为了研究氟尼辛葡甲胺对患呼吸道疾病奶牛的解热效果,试验选75头患呼吸道疾病泌乳期的奶牛并分为5个组,分别为高剂量组(氟尼辛葡甲胺4.4 mg/kg·bw土霉素20 mg/kg·bw)、中剂量组(推荐剂量,氟尼辛葡甲胺2.2 mg/kg·bw土霉素20 mg/kg·bw)、低剂量组(氟尼辛葡甲胺1.1 mg/kg·bw土霉素20 mg/kg·bw)、药物对照组(福乃达2.2 mg/kg·bw土霉素20 mg/kg·bw)和土霉素组(20 mg/kg·bw),每组15头奶牛。在给药前和最后一次给药后的第1、2、3、7天和14天分别记录奶牛的直肠温度、呼吸频率、食欲、呼吸困难以及咳嗽情况,并依据评分表进行打分。结果在最后一次给药后的第1、2、3、7天和14天,高剂量组、中剂量组和药物对照组之间,直肠温度无显著差异(P>0.05);在最后一次给药后的第14天,高剂量组与中剂量组均比土霉素组在降低动物直肠温度方面具有更显著的效果(P≤0.05)。最后1次给药后的第14天,高剂量组、中剂量组与土霉素组相比,临床症状得分降低更显著(P≤0.05);高剂量组、中剂量组、低剂量组与药物对照组相比,临床症状得分虽然无显著性差异(P>0.05),但是临床症状得分数值上,高剂量组、中剂量组均略低于药物对照组。在最后1次给药后的第14天,高剂量组、中剂量组、低剂量组、土霉素组和药物对照组对奶牛呼吸道疾病的治愈率分别为80.00%、73.33%、60.00%、53.33%和66.67%。结论:建议氟尼辛葡甲胺注射液临床上用于治疗呼吸道疾病引起的奶牛高热时,给药方式为静脉给氟尼辛葡甲胺注射液2.2 mg/kg·bw,每日1次,连用5 d,并单次肌肉注射土霉素注射液20 mg/kg·bw,连用5 d。     

一种动物专用解热镇痛抗炎药--氟尼辛葡甲胺

氟尼辛葡甲胺(flunixin meglumine)是一种有效的非麻醉、非类固醇类的止痛剂(NSAID’S)，最早由Doran；Henry等人于1996年研制生产(U．S．P NO．5484931)，美国先灵葆雅公司将其做成注射液(商品名为Banamine)，用于动物疾病的治疗。由于其疗效好、毒性低，在欧美等国家应用广泛，并于2004年10月被FDA批准用于产乳期奶牛。本文简要介绍一下该药。     

奶牛产后注射氟尼辛葡甲胺对乳房炎发生率的影响

氟尼辛葡甲胺在缓解分娩疼痛、促进奶牛产后生理代谢功能恢复、预防围产后期代谢病方面有一定效果。为探讨奶牛产后注射氟尼辛葡甲胺对奶牛乳房炎发生率的影响,笔者选取50头经产母牛分为两组进行了临床试验,并对北京郊区某奶牛场使用氟尼辛葡甲胺注射液前后奶牛乳房炎发生情况进行了统计比较。结果表明奶牛产后注射氟尼辛葡甲胺可一定程度上降低奶牛乳房炎的发生率。     

新兽药氟尼辛葡甲胺的解热镇痛作用

通过小鼠醋酸扭体法、家兔蛋白胨致热法对氟尼辛葡甲胺的解热、镇痛作用进行了研究。结果表明,氟尼辛葡甲胺具有明显的解热、镇痛作用。和对照组相比,氟尼辛葡甲胺4个剂量组（1.25、2.5、5、10 mg/kg）对醋酸所致的小鼠扭体反应均有极强的抑制作用,抑制率最高达100%。2.5 mg/kg的氟尼辛葡甲胺镇痛率即达82.7%,明显强于双氯芬酸钠（65.4%）和安乃近（58.7%）。对蛋白胨所致家兔发热的解热效果,氟尼辛葡甲胺高剂量组（4 mg/kg）优于安乃近组（0.2 g/kg）（P〈0.05）和氨基比林组（0.2 g/kg）（P〈0.01）。中剂量氟尼辛葡甲胺组（2 mg/kg）作用稍逊于安乃近组,但差异不显著。低剂量氟尼辛葡甲胺组（1 mg/kg）作用与氨基比林组相当。     

氟尼辛葡甲胺

1理化性质及作用机制氟尼辛葡甲胺的分子量为491．46,熔点为137～140℃。性状为白色至类白色粉末,在水或乙醇中易溶,在氯仿中难溶。     

新兽药氟尼辛葡甲胺的研究

氟尼辛葡甲胺（Flunixin meglumine），是美国先灵葆雅公司于20世纪90年代开发的业经批准的少数兽用非甾体类药物之一，主要通过抑制环氧化酶、减少前列腺素等炎性介质的生成而发挥解热、抗炎和镇痛作用。该药最早用于缓解马的炎症和肌肉，骨骼紊乱及绞痛等相关疼痛，随后被批准用于牛传染病引起的急性炎症、母猪无乳综合征的辅助治疗和犬的内毒素血症等，现已在英国、法国、瑞士、德国、美国等许多国家广泛应用。     

Effects of ketoprofen and flunixin in pigs experimentally infected with Actinobacillus pleuropneumoniae

The antipyretic effect of the non-steroidal anti-inflammatory drugs (NSAIDs) ketoprofen (3 mg/kg) and flunixin (2 mg/kg) were studied in pigs. The drugs were administered intramuscularly at 8 and 32 h following endobronchial challenge with Actinobucillus pleuropneumoniae. Infected (non-medicated) and non-infected (non-medicated) controls were used. Endobronchial challenge with Actinobucillus pleuropneumoniae induced laboured breathing, coughing, fever, reduced food and water consumption and increased white blood cell counts. At autopsy, pleuropneumonia was evident. Ketoprofen showed a highly significant antipyretic effect but flunixin did not. The decrease in food consumption of ketoprofen-treated pigs was significantly less than that of the infected (non-medicated) controls. Blood parameters were not significantly influenced by either NSAID and, at necropsy, gastric and renal side-effects were not observed for either drug.     

Effects of flunixin meglumine in dogs following experimentally induced endotoxemia

Twelve dogs were randomly divided into three groups. Group 1 dogs were given Escherichia coli endotoxin and then treated with flunixin meglumine. Group 2 dogs were given endotoxin as group 1, but untreated. Group 3 dogs were given flunixin meglumine alone. The dogs were monitored clinically and urine and serum samples were collected at regular intervals for 72 hours. All surviving dogs were humanely killed after 72 hours and examined for gross and histologic lesions. Group 1 dogs all survived 72 hours, but showed prerenal azotemia, hepatocellular damage, hemorrhagic enteritis, and numerous gastric ulcerations. Three of the four dogs in group 2 died before 72 hours. Group 2 dogs showed many of the same chemical and hemodynamic changes as group 1. They had severe hemorrhage into the intestinal lumen; however, there were no gastric ulcerations. Group 3 dogs all survived and showed little physical or hematologic change. The study suggested the following: 1) flunixin meglumine was an effective drug in ameliorating the fatal effects of canine endotoxemia, 2) the effects of endotoxin in combination with flunixin meglumine, at 1.1 mg/kg body weight, caused gastric ulcerations, and 3) in normal dogs flunixin meglumine at 1.1 mg/kg body weight did not cause severe side effects or gross lesions.     

Pharmacokinetics of ampicillin and sulfadimidine in pigs infected experimentally with Streptococcus suum

Twenty-three hybrid pigs (23 ± 3 kg body wt) were assigned to three groups to investigate the pharmacokinetics of ampicillin (APC, 10 mg/kg) administered intravenously (i.v.) and intramuscularly (i.m.), and sulfadimidine (SDM, 50 mg/kg) administered intravenously as a bolus injection. In the first series of experiments the animals remained healthy. Subsequently, the pigs were infected with Streptococcus suum by subcutaneous (s.c.) inoculation and the experiments were repeated. The total apparent distribution volume of APC given intravenously was increased from 0.512 ± 0.026 L/kg in uninfected pigs to 0.68 ± 0.06 L/kg (P < 0.01) in infected pigs, whereas there were no significant changes in the same parameter for SDM (P > 0.05). The clearance of APC was increased markedly from 0.52 ± 0.07 L/kg/h in uninfected pigs to 0.62 ± 0.10 L/kg/h in infected pigs. In contrast, SDM clearance was decreased markedly from 0.023 ± 0.003 L/kg/h to 0.017 ± 0.003 L/kg/h (P < 0.05). As a result, the biological half-lives of the drugs were altered to varying degrees in infected pigs. The half-life of SDM was increased from 15.0 ± 3.0 h in uninfected pigs to 20 ± 7h in infected pigs (P < 0.05), but differences in APC half-lives between uninfected and infected animals were not observed (P > 0.05). There were no statistically significant differences in pharmacokinetic parameters of APC administered by intramuscular injection between the healthy and the diseased status, although its half-life was shortened from 0.76 ± 0.22 h in the healthy to 0.57 ± 0.23 h in the diseased. The results suggest that blood concentrations of APC and SDM are affected differently by the same disease due to its specific effects on their distribution and elimination.     

Flunixin对猪肝微粒体细胞色素P450酶系的影响

采用cocktail探针药物法研究了氟尼辛葡甲铵对猪肝微粒体细胞色素（CY）P450酶系的作用.将12头猪随机分为2组,试验组每日肌肉注射氟尼辛葡甲铵1次,对照组给予等体积的生理盐水,连续给药10 d.通过高效液相色谱法检测探针药物的代谢率,评价各组CYP450酶的活性水平.结果显示,试验组的氨苯砜代谢减慢,消除半衰期t1/2延长;而氯唑沙宗代谢加快,t1/2缩短.说明氟尼辛葡甲铵对猪的CYP3A4具有抑制作用,而对CYP2E1存在诱导效应.     

Pharmacokinetics of flunixin meglumine in dogs

The pharmacokinetics of flunixin meglumine, a potent nonsteroidal anti-inflammatory agent, were studied in 6 intact, awake dogs. Plasma samples were obtained up to 12 hours after IV administration of flunixin meglumine. Flunixin concentration was determined, using high performance liquid chromatography. Plasma data best fit a 2-compartment model. Distribution half-life was 0.55 hour; elimination half-life was 3.7 hours; volume of distribution (area) was 0.35 L/kg; volume of distribution at steady state was 0.18 L/kg; volume of the central compartment was 0.079 L/kg; and total body clearance was 0.064 L/hr/kg. Flunixin concentrations obtained over a 6-hour period in 3 dogs with septic peritonitis did not differ significantly from those obtained from healthy dogs.     

探针药物法评价氟尼辛葡甲铵对猪肝CYP450酶的影响

采用Cocktail探针药物法探讨氟尼辛葡甲铵对猪肝CYP450酶是否具有诱导或抑制作用。将12头健康猪随机均分为2组,公母各半。试验组每天肌肉注射氟尼辛葡甲铵1次（11 mg/kg）,对照组给予相同体积的生理盐水,连续给药10 d。通过HPLC检测探针药物的代谢率,来评价各组CYP450水平。结果显示,试验组的氨苯砜代谢减慢,t1/2延长;而氯唑沙宗代谢加快,t1/2缩短。这说明氟尼辛葡甲铵对猪CYP3A4具有抑制作用,而对CYP2E1存在诱导效应。     

Pharmacokinetics of flunixin meglumine in the cow

Plasma levels of flunixin were measured in heifers after a single intravenous injection (1.1 mg kg-1), using high performance liquid chromatography. Plasma concentration versus time curves were best described by a two compartment model. The distribution phase (alpha) half-life was 0.294 hours, the elimination phase (beta) half-life was 8.12 hours and the volume of distribution was 1050 ml kg-1.     

Efficacy and pharmacokinetics of enrofloxacin and flunixin meglumine for treatment of cows with experimentally induced Escherichia coli mastitis

The efficacy of flunixin alone and together with enrofloxacin in treatment of experimental Escherichia coli mastitis was compared using six cows. The cross-over study design was used. Pharmacokinetics of flunixin and enrofloxacin were also studied in these diseased cows. The response of each cow was similar after the first and second challenge and the individual reaction seemed to explain the severity of clinical signs. The most important predictive factor for outcome of E. coli mastitis was a heavy drop in milk yield. Treatment with enrofloxacin and flunixin enhanced elimination of bacteria, but the difference from those receiving flunixin alone was not significant. Two cows, which had received no antimicrobial treatment (Group 1), were killed on day 4 postchallenge. One cow was killed after the first and the other after the second challenge. Cows receiving combination therapy produced 0.9 L more milk per day during the study period than cows which had only received flunixin (P < 0.05). Based on our findings, antimicrobial treatment might be beneficial in the treatment of high-yielding cows in early lactation. The absorption of enrofloxacin was delayed after subcutaneous administration, the mean apparent elimination half-life being about 23 h, whereas after i.v. administration elimination t(1/2) was only 1.5 h. The majority of the antimicrobial activity in milk originated from the active metabolite, ciprofloxacin, which could be measured throughout the 120-h follow-up period after the last subcutaneous administration. No differences were present in the pharmacokinetic parameters of flunixin between treatment groups: mean elimination half-life was 5.7-6.2 h, volume of distribution 0.43-0.49 L/kg and clearance 0.13-0.14 L h/kg. No flunixin or merely traces were detected in milk: one of the three cows had a concentration of 0.019 mg/L 8 h after administration.