【作者】 刘芳萍；

【导师】 佟恒敏；

【作者基本信息】 东北农业大学 ， 基础兽医学， 2001， 硕士

【摘要】 单诺沙星是一种动物专用的氟喹诺酮类药物。本课题以高效液相色谱（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及口服给药的生物利用度；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。由单剂量给药参数，算出多剂量给药参数，为单诺沙星的临床应用提供理论依据。 采用MCP-KP自动化药动学分析程序对血药数据进行分析。药动学分析结果表明，雏鸡单剂量静脉注射单诺沙星后（5mg/kg），血药经时过程符合无吸收因素二室开放式模型，主要药动学参数为：t_1/2α0.3313±0.0966h、t_1/2β5.9940±1.4089h、V_d7.5246±0.7515 1/kg、AUC5.6916±0.8178μg/ml.h、CL_B0.8935±0.1311l/kg.h。其理论方程为：C=1.3995e^-2.2379t+0.5947e^-0.1208t。 雏鸡单剂量口服单诺沙星后（5mg/kg），血药经时过程符合一级吸收一室开放式模型，主要药动学参数为：t_1/2Kα0.3029±0.1754h、t_1/2K6.5128±3.7449h、t_max 1.2100±0.4364h、C_max0.5159±0.0399μg/ml、AUC 5.1329±1.2849μg/ml.h，生物利用度为90.18％。其理论方程为C=0.5598(e^-0.1286t-e^-3.3152t)。 体外抑菌实验测得单诺沙星在体外对大肠杆菌、金葡球菌的最低抑菌浓度（MIC）均为0.25μg/ml。以三种不同浓度的单诺沙星测定在体外对大肠杆菌、金葡球菌的抗菌后效应（PAE），结果如下，浓度分别为0.5MIC、2MIC、4MIC的单诺沙星对大肠杆菌的PAE测定值分别为0.6464±0.0294h、1.2077±0.0284h、1.6529±0.0496h，对金葡球菌的PAE测定值分别为0.5660±0.0075h、1.1746±0.0057h、1.4913±0.0257h。 药动学研究结果表明，单诺沙星口服给药后，吸收迅速，体内分布广泛，消除半衰期长，生物利用度高，吸收效果良好等特点；PAE研究结果表明，单诺沙星对大肠杆菌、金葡球菌均有不同程度的较强的PAE。结合口服给药的药动学参数和体外PAE值，提出了合理的给药方案，雏鸡口服单诺沙星每日一次。更多还原

【Abstract】 Danofloxacin is one of the floroquinolones only used for animals infectious diseases. The pharmacokinetic characteristics and bioavailability of danofloxacin following intravenous and oral administration were conducted with chicken by using the (High performance liquid chromatography , HPLC) interal method in this study. The post-antibiotic effects (PAE) of danofloxacin in vitro against E. coli and S. aureus were tested by routine colonial counting method. And the multiple-dose pharmacokinetic parameters were assessed according to the single-dose pharmacokinetic parameters, so this can provide bases for the clinical uses of danofloxacin.The data were analyzed with the pharmacokinetic computer program MCP-KP. The pharniacokinetics showed that the plasma concentration-time course of danofloxacin by intravenous administration (5mg/kg) can be described by a two-compartment open model. The main pharmacokinetics parameters were as follows: tii2a0.33l3~0.0966h t112~5.9940~1.4089h .~ Vd7.5246*0.7515l/kgAUC5.6916~0.8178~ig/ml~h~ CLB0.8935~0.1311l/kg~h.The theoretical equation was as follows: C=1.3995e?3+0.5947&0 .1203:The concentration-time course of danofloxacin in plasma following oral administration (5mg/kg) in chicken can be described by one-compartment open model with first-order absorption. The primary parameters were showen below:tI/2Ka 0.3029~0.1754h~ tI/2K 6.5128~3.7449h tmax 1.2l00~0.4364 h~ Cmax 0.5l59~0.0399p.tg/ml AUC 5.l329~1.2849j.tg/mlh . The bioavailability was0 1236:3 3152t90.18%. The theoretical equation was as follows: C0.5598(& -&The inhibited experiment in vitro showed that the minimum inhibited concentration(MIC) of both E.coli and S.aureus was 0.25jig/ml. The post-antibiotic effects (PAE) of danofloxacin against E.coli and S.aureus in vitro at three different concentration levels were tested by routine colonial counting method. The PAE of danofloxacin against E.coli and S.aureus in vitro at the concentration levels of 0.5MIC, 2MIC and 4MIC were 0.6464~0.0294h~ l.2077~0.0284h~ 1.6529*0.0496h for E.coli, and 0.5660~0.0075h~ 1.1746~0.0057h. 1.49l3h for S.aureus respectively.The results of pharmacokinetic investigation show that after danofloxacin taking orally in chicken , it has many characteristics ,for example , it can be absorbed quickly , the distribution invitro is widespread; the precluding half time is long ; the bioavailability is excellent , the effect of absorption is well ; and so on The results showed that the PAE of danofloxacin against E.coli and S.aureus was more stronger. So binding the pharmacokinetic characteristics of danofloxacin following oral administration and the PAE in vitro , we suggest that the reasonable administration project is that the chicken can take danofloxacin once one day with oral adminstration.Postgraduate: Liu FangpingMajor: Basic Veterinary MedicineTutor:Prof. Tong Hengmin更多还原