【作者】 王加才；

【导师】 江善祥；

【作者基本信息】 南京农业大学 ， 基础兽医学， 2006， 硕士

【摘要】 氟苯尼考是一种氯霉素类的广谱抗生素，在兽医临床上应用广泛。本课题研究了氟苯尼考超微粉的制备及其在肉鸡体内的药动学与药效学。具体研究内容如下： 1 氟苯尼考超微粉的制备 利用TC-10型流化床超音速粉碎分级机系统对氟苯尼考进行超微粉碎化处理，药物颗粒的粒径减小、表面积成倍增加，氟苯尼考的体内生物利用度和水中溶解度显著提高。试验结果表明，超微粉碎400目、600目和800目与未粉碎药物（60目）比较，溶解度分别增加2.84倍、3.17倍和3.24倍，差异极显著（P＜0.01）。粉碎600、800目与粉碎400目比较溶解度增加显著（P＜0.05），但粉碎600目与800目比较差异不显著（P＞0.05）。在粉碎相同目数的情况下，氟苯尼考与载体的比例对氟苯尼考溶解度的影响不显著。药物的稳定性试验结果表明，超微粉经葡萄糖稀释后，室温密封保存0～180d，药物含量稳定、性状无显著变化。 2 氟苯尼考超微粉在肉鸡体内的药动学研究 以30mg／kg单剂量内服氟苯尼考超微粉和原粉，研究了其在健康和大肠杆菌感染肉鸡体内的药代动力学。肉鸡单次内服氟苯尼考超微粉和原药后，血药浓度和时间关系均符合一室开放模型，选择的权重为1／C²。健康组肉鸡的主要药代动力学参数：氟苯尼考超微粉组和原药组的t_1／2ka分别为23.49±4.48min和28.89±4.51min，t_1／2ke分别为104.57±16.25min和101.66±9.97min，Tmax分别为62.23±4.78min和72.86±7.15min，Cmax分别为8.65±0.67μg·ml^-1和7.94±0.78μg·ml^-1，AUC分别为36.87±3.63μg·ml^-1·h和33.01±7.73μg·ml^-1·h。氟苯尼考超微粉和原药在健康肉鸡体内吸收迅速，分布广泛，峰浓度较高，同时在体内的消除也较快。氟苯尼考超微粉在健康肉鸡体内的主要药代动力学参数t_1／2ka、Tmax和Cmax与原药比较差异显著（P＜0.05），t_1／2ke差异不显著。说明药物经超微粉碎后在体内的吸收速率加快，血药浓度更高。以氟苯尼考原药作为标准，则超微粉在肉鸡体内的相对生物利用度为111.69％。大肠杆菌感染肉鸡的主要药动学参数：氟苯尼考超微粉和原药的t_1／2ka分别为24.00±4.95min和33.09±9.76min，t_1／2ke分别为112.06±17.08min和108.14±17.41min，Tmax分别为66.00±15.29min和74.23±10.70min，Cmax分别为8.49±1.22μg·ml^-1和7.84±0.94μg·ml^-1，AUC分别为38.82±8.93μg·ml^-1·h和32.02±3.70μg·ml^-1·h。肉鸡感染大肠杆菌后药物在体内仍能较快地吸收分布。氟苯尼考超微粉在感染肉鸡体内的主要药代动更多还原

【Abstract】 Preparation of florfenicol ultrafine powder and its pharmacokinetics and pharmacodynamics in chickens were studied in this paper.1 Preparation of florfenicol ultrafine powderFlorfenicol ultrafine powders were prepared by the TC — 10 type ultrasonic pulverizator system. The granule of florfenicol was decreased in size and the face area was augmented. The bioavailability and solubility in water were increased significantly. The result showed that the solubility of three sizes of 400 sieve, 600sieve and 800sieve was increased by 2.84, 3.17 and 3.24 times respectively than the solubility of 60 sieve （P<0.01）. The solubility of 600 sieve and 800 sieve was significantly different compared with the 400 sieve. However, there was no difference between 600 sieve and 800 sieve. The solubility of ultrafine powder with two carriers was not increased significantly. The result of the study on stability showed that the properties and content of the ultrafine-powder didn’t changed significantly for 180 days at airproof station with room temperature.2 Study on pharmacokinetics of florfenicol ultrafine-powder in chickensPharmacokinetics of florfenicol ultrafine-powder and florfenicol powder were studied on healthy and experimentally E.coli infected broiler chickens following single oral administration at a dose of 30mg·kg^-1. The kinetic disposition followed a one-compartment open model after a single oral administration of florfenicol ultrafine-powder and florfenicol powder in healthy and E.coli infected broiler chickens with weight by 1/C². The main pharmacokinetic parameters of florfenicol ultrafine-powder and florfenicol powder in healthy broiler chickens were as follows: t_1/2ka 23.49±4.48min and 28.89±4.51min, t_1/2ke更多还原