达氟沙星对猪胸膜肺炎放线杆菌的体外药效研究

为了解猪胸膜肺炎放线杆菌对达氟沙星的敏感性和达氟沙星的杀菌效果,收集和分离48株猪胸膜肺炎放线杆菌,采用微量肉汤稀释法和菌落计数法对体外药物敏感性试验和生长曲线、杀菌曲线进行了研究。猪胸膜肺炎放线杆菌对氨苄西林、磺胺异恶唑、头孢噻呋、大观霉素、黏菌素耐药率高,对阿莫西林/克拉维酸、复方新诺明、氟苯尼考、多西环素、庆大霉素、四环素、恩诺沙星、氧氟沙星、达氟沙星敏感。达氟沙星最小抑菌浓度(MIC)集中在0.0078μg/m L。达氟沙星浓度在MIC及以上时,随浓度升高,杀菌时间缩短,为典型的浓度依赖型抗生素。该试验结果可用于指导猪传染性胸膜肺炎的临床预防和治疗。     

单诺沙星在蛋雏鸡体内的药物动力学及生物利用度的研究

选用 4～ 5周龄健康蛋雏鸡 12 5只 ,按 5 mg/kg的剂量进行静脉注射和内服单诺沙星的药动学研究及生物利用研究。高效液相色谱内标法测定血浆中药物浓度 ,MCPKP药动学程序处理药时数据。静脉注射和内服给药后血药浓度—时间数据分别符合无吸收因素二室开放式模型和一级吸收一室开放式模型。静脉注射给药的主要药动学参数为 :t1 /2α=0 .3313h、t1 /2β= 5 .994 0 h、Vd=7.5 2 4 6 L/kg、AU C=5 .6 916 μg/m l· h、CLB=0 .8935 L/kg· h。内服给药后主要药动学参数为 :t1 /2 Ka=0 .30 2 9h、t1 /2 K=6 .5 12 8h、tmax=1.2 10 0 h、Cmax=0 .5 15 9μg/m l、AU C=5 .132 9μg/ml· h。生物利用度为 90 .18%。     

单诺沙星在雏鸡体内的药动学及其抗菌后效应研究

本论文以高效液相色谱(HPLC)内标法为定量手段,研究了单诺沙星经静注、口服两种途径给药后在雏鸡体内的药物代谢动力学特征;以菌落计数法测定了单诺沙星对大肠杆菌、金黄色葡萄球菌(金葡球菌)的体外抗菌后效应。静注和内服给药后血药浓度-时间数据分别符合无吸收因素二室开放式模型和一级吸收一室开放式模型。静注给药的主要药动学参数为:t1/2α0.3313h、t1/2β5.9940h、Vd7.5246L/kg、AUC5.6916μg/(mL·h)、CLB0.8935/(kg·h)。内服给药后主要药动学参数为:t1/2Ka0.3029h、t1/2K6.5128h、tmax1.2100h、Cmax0.5159μg/mL、AUC5.1329μg/(mL·h),生物利用度为90.18%。抗菌后效应(PAE)结果如下,浓度分别为0.5MIC、2MIC、4.MIC的单诺沙星对大肠杆菌的PAE测定值分别为(0.6464±0.0294)h,(1.2077±0.0284)h,(1.6529±0.0496)h,对金葡球菌的PAE测定值分别为(0.5660±0.0075)h,(1.1746±0.0057)h,(1.4913±0.0257)h。     

单诺沙星对人工诱发鸡大肠肝菌病的药效试验

根据试管 2倍稀释法测定的单诺沙星及氯霉素对鸡大肠杆菌的最小抑菌浓度 ,对实验性大肠杆菌病鸡进行内服给药 (每隔 12h给药 1次 ,连续 3d)治疗试验。结果表明 ,单诺沙星及氯霉素对鸡大肠杆菌的最小抑菌浓度分别是 0 0 5及 1 6mg/L。单诺沙星以 5mg/kg、氯霉素以40mg/kg的剂量给鸡内服后 ,对大肠杆菌病的治愈率分别为 87 5%及 55 0 %。     

达氟沙星对试验性感染仔猪副伤寒和霉形体肺炎的药效学研究

研究了国产新兽药达氟沙星对人工感染仔猪伤寒和霉形体肺炎的疗效。每个疗效试验用仔猪105只，随机分为达氟沙星3个不同剂量组，恩诺沙星对照组，强力霉素对照组，阳性对照组和阴性对照组，每组动物15只。当感染猪出现典型症状时，达氟沙星3个剂量组分别按每千克体重2．5ml,1.25mg,0.625mg，0.625mg及恩诺沙星组按2．5mg肌肉注射，每日2次，强力霉素按每千克体重3mg肌肉注射，每日2次。结果表明：达氟沙星3个不同剂量组、恩诺沙星组、强力霉素组连续用药4d，对仔猪副伤寒的治愈率分别是100％、80％、33．3％、80％、53．3％、而感染（阳性）对照组的死亡率为66．7％；达氟沙星3个不同剂量组、恩诺沙星组、强力霉素组连续用药5d,对霉形体肺炎的治愈率分别是100％、80％、93．3％，肺部病变率分别是20％、40％、60％、20％、60％，而感染（阳性）对照组的死亡率为40％，肺部病变率为1005。     

三种兽用氟喹诺酮类药物对人工诱发鸡霍乱的疗效比较

采用试管肉汤两部类法,测得恩诺沙星、单诺沙星脑二氟沙星对鸡多杀性巴氏杆菌的最小抑菌质量浓度分别是０．０５、０．２及０．４ｍｇ／Ｌ,按５ｍｇ／ｋｇ的剂量,分别给人工诱发霍乱病鸡内服恩诺沙星、单诺沙星脏一氟沙星,每１２ｈ给药１次,连续３ｄ,这些药物对鸡霍乱的治愈率分别为９６．７％、８３．３％及８３．３％。而感染对照鸡的死亡率为１００％。     

鲫血浆中甲磺酸达氟沙星的RP-HPLC法测定

建立了测定鲫血浆中甲磺酸达氟沙星浓度的反相高效液相色谱法(RP-HPLC).采用ZORBAX SB-C18色谱柱和SB-C18的保护柱;流动相:乙腈与磷酸盐缓冲液(含10 mmol.L-1磷酸二氢钠和15 mmol.L-1四丁基溴化铵,磷酸调节pH4.0)的体积比为8∶92;流速:1.0 mL.min-1;进样量:10μL;柱温:30℃;检测波长282 nm.内标物为盐酸氧氟沙星.本研究建立的甲磺酸达氟沙星标准曲线在0.05~5.00 mg.L-1范围内呈良好的线性关系(R=0.999 9),最低检测限为0.01 mg.L-1,提取回收率均大于80%,日内及日间相对标准偏差小于11%.     

Some Pharmacokinetic Data for Danofloxacin in Healthy Goats

The pharmacokinetics of danofloxacin was determined in five clinically normal adult female goats after intravenous (IV) or intramuscular (IM) doses of 1.25 mg/kg body weight. Blood and urine samples were collected from each animal at precise time intervals. Serum and urine concentrations were determined using microbiological assay methods and the data were subjected to kinetic analysis. After intravenous injection, the serum concentration–time curves of danofloxacin were characteristic of a two-compartment open model. The drug was rapidly distributed and eliminated with half-lives of 17.71±1.38 min and 81.18±3.70 min, respectively. The drug persisted in the central, highly perfused organs with a K ₁₂/K ₂₁ ratio of 0.67±0.25. The mean volume of distribution at a steady state (V _dss) was 1.42±0.15 L/kg. After intramuscular administration, the serum concentration peaked after 0.58±0.04 h at approximately 0.33±0.01 g/ml. While danofloxacin could be detected in serum for 4 and 6 h, it was recovered in urine for up to 24 and 72 h after IV and IM administration, respectively. The systemic bioavailability after IM injection was 65.70%±10.28% and the serum protein-bound fraction was 13.55±1.78%.     

Population pharmacokinetics for danofloxacin in the intestinal contents of healthy and infected chickens

Avian pathogenic Escherichia coli could cause localized and systemic infection in the poultry, and danofloxacin is usually used to treat avian colibacillosis through oral administration. To promote prudent use of danofloxacin and reduce the emergence of drug‐resistant E. coli strains, it is necessary to understand the population pharmacokinetics (PopPK) of danofloxacin in chicken intestines. In this study, reversed‐phase high performance liquid chromatography (HPLC) with fluorescence detection was used to detect the concentrations of danofloxacin in the contents of duodenum, jejunum, and ileum of the healthy and infected chickens after single oral administration (5 mg/kg body weight). Then, the PopPK of danofloxacin in intestines were analyzed using NONMEM software. As a result, a two‐compartment PK model best described the time‐concentration profile of duodenal, jejunal, and ileal contents. Interestingly, absorption rate (K_a), distribution volume (V), and clearance (CL) for danofloxacin from duodenal, jejunal to ileal contents were sequentially decreased in the healthy chickens. However, the trend of K_a, V, and CL of danofloxacin was changed dramatically in the intestine of infected chickens. K_a and V of danofloxacin in the jejunum were higher than in the ileum and duodenum. Compared with healthy chickens, K_a and V of danofloxacin in the duodenum decreased significantly, while increased in jejunum, respectively. It has been noted that K_a decreased and V increased in the ileum of infected chickens. Besides, CL in the duodenum, jejunum, and ileum of infected chickens was, respectively, lower than those of healthy chickens. Interestingly, the relative bioavailability (F) of danofloxacin in the ileum was relatively higher in both healthy and infected chickens. In addition, F in the duodenal, jejunal, and ileal contents of infected chickens was respectively higher than healthy chickens. In summary, the PopPK for danofloxacin in infected chicken intestines was quite different from healthy chickens. The absorption, distribution, and clearance of danofloxacin in healthy chickens decreased from duodenum to jejunum and to ileum. Moreover, the pharmacokinetic characteristics in the intestine of infected chickens changed significantly, and the pharmacokinetic characteristics in the ileum can be used as a representative of all intestinal segments.     

单诺沙星对昆明种小白鼠的亚急性毒性研究

以昆明种小白鼠为实验研究，进行了单诺沙星的亚急性毒性研究。小白鼠分为4组，1－3组为试验组，分别以20，50，100mg/kg体重单诺沙星溶于饮水中连续给药一个月，第4组为对照组。实验期间定期称量小白鼠在给药期内的体重和采食量，计算食饵效率，并在给药半个月和一个月时分两次检查各组小白鼠的器官系数与器官含水量、血常规、肝肾功能指标GPT、GOT、AKP、Cr、BUN以及心、肝、脾、肺、肾、脑的病理组织学变化。实验结果表明：高剂量组小白鼠表现的毒性反应较轻，且这种毒性反应没有随时间的延长而加剧。中、低剂量组小白鼠没有出现明显的毒性反应。表明单诺沙星的毒性较低。