头孢噻呋在麻鸡体内的药代动力学研究

发布时间：2018-04-23 18:14

本文选题：头孢噻呋钠 + 高效液相色谱法　；参考：《山东农业大学》2017年硕士论文

【摘要】：二十世纪八十年代,美国法玛西亚-普强公司(PharmaciaUpjohn)开发了畜禽专用头孢菌素,即头孢噻呋(Ceftiofur),又名赛得福。头孢噻呋为第三代头孢菌素,抗菌机理是通过抑制细菌细胞壁的合成导致细菌死亡,头孢噻呋对链球菌的抗菌作用比氟喹诺酮类药物强,抗菌活性优于氨苄西林。头孢噻呋自诞生以来,因其具有抗菌谱广,抑制或杀灭病原微生物的能力强,毒副作用低,残留少等优势,获得世人的认可接受,头孢噻呋被批准应用于动物细菌性疾病的治疗。自1988年以来,头孢噻呋钠先后被北美、欧洲一些国家及日本正式批准用于猪、羊、奶牛、肉牛、马的呼吸道疾病治疗和宠物感染性疾病的防治。目前,我国家禽养殖已走向规模化,养殖密度大、环境差,易导致畜禽传染性疾病流行和爆发,由此可能引发禽类大批量出现疫情甚至死亡的现象,将会给养禽业造成巨大损失。头孢噻呋钠作为动物专用的一种新抗生素,在一定程度上解决了养禽场细菌性疾病所引发的问题。随着国内企业成功合成头孢噻呋钠并大批量生产,其合成原料成本不断降低,头孢噻呋钠在兽药领域将得到更加广泛的应用。与此同时,对于头孢噻呋钠能否在不同种属畜禽体内得到科学、合理和安全的应用,也将此药在多种动物体内外的研究引向深入。通过运用高效液相色谱法(HPLC)检测麻鸡体内头孢噻呋钠的浓度,研究头孢噻呋钠在麻鸡体内的药动学行为,从而清晰的判断和了解头孢噻呋钠在麻鸡的机体内ADME过程,同时能够更加科学的确定头孢噻呋钠的给药途径、给药时间,建立测定头孢噻呋钠的药代动力学及组织分布的研究方法,从而为临床上安全、合理的用药,以及制定休药期、防止药物残留提供参考。试验分别采用口服和肌肉注射的给药方式研究头孢噻呋钠在麻鸡体内的药动学过程,给药后不同的时间点进行麻鸡翅下静脉采血,采用HPLC对血浆样品和组织样品进行头孢噻呋钠原型药物的检测分析,对头孢噻呋钠在麻鸡体内的药代动力学特点进行研究、对头孢噻呋钠在麻鸡体内的生物利用度进行分析。通过对头孢噻呋钠在麻鸡体内的药代动力学测定研究发现,对麻鸡经肌注给予头孢噻呋钠20 mg/kg的原型药代动力学参数:血浆达峰浓度Cmax为(6.337±3.29)μg/mL,达峰时间Tmax为(0.25±0.00)h,消除半衰期t1/2为(0.851±0.23)h,消除速率常数Ke为(0.883±0.32)h-1,AUC0-t为(5.338±2.85)μg·h·mL-1,AUC0→∞为(5.417±2.87)μg·h·mL-1,平均滞留时间MRT为(0.837±0.07)h,清除率CLtot为(72.950±28.53)m L·min-1·kg-1,表观分布容积Vd为(5.250±2.20)L·kg-1。麻鸡肌注头孢噻呋钠在其组织中未检测到头孢噻呋钠原型药物。通过对麻鸡口服给予头孢噻呋钠20 mg/kg的药动学研究发现:麻鸡口服头孢噻呋钠在其血液及组织均未检测到头孢噻呋钠原型药物,表明头孢噻呋钠口服不吸收。
[Abstract]:In 1980s, the American The Upjohn Company (PharmaciaUpjohn) developed livestock and poultry cephalosporin, namely ceftif (Ceftiofur), also known as ceftif. Ceftif is the third generation cephalosporin. The antibacterial mechanism is to inhibit bacterial death by inhibiting the synthesis of bacterial cell wall, and the antibacterial action of ceftif to Streptococcus Fluoroquinolones are strong and antibacterial activity is superior to ampicillin. Since its birth, ceftif has been accepted by the world because of its strong antibacterial spectrum, strong ability to inhibit or kill pathogenic microbes, low toxicity and few residues. Ceftif has been approved for the treatment of bacterial diseases in animals. Since 1988, ceftif TIF sodium has been officially approved by North America, some European countries and Japan for the treatment of respiratory diseases of pigs, sheep, cows, beef cattle, horses and the prevention and treatment of infectious diseases of pets. At present, poultry breeding in China has become large-scale, the density is large and the environment is poor, which may lead to the epidemic and outbreak of infectious diseases of livestock and poultry, which may cause a large number of poultry. The occurrence of epidemic situation and even death will cause great loss to poultry industry. As a new antibiotic, ceftif sodium has solved the problems caused by bacterial disease in poultry farm to a certain extent. With the successful synthesis of ceftif sodium in domestic enterprises and mass production, the cost of synthetic raw materials is decreasing. Ceftif sodium will be more widely used in the field of veterinary medicine. At the same time, the scientific, rational and safe application of ceftif sodium in different species of livestock and poultry is used, and the study of the drug in and out of a variety of animals is also introduced. The use of high performance liquid chromatography (HPLC) for the detection of ceftif sodium in the chicken body Concentration, study the pharmacokinetics of ceftif sodium in the chicken, so as to clearly determine and understand the ADME process in the body of ceftif sodium in the body of the chicken. At the same time, it can be more scientific to determine the route of administration of ceftif sodium, the time of administration, and establish a method for the determination of the pharmacokinetics and tissue distribution of ceftif sodium, and the method of the study of the pharmacokinetics and tissue distribution of ceftif sodium. The pharmacokinetic process of ceftif sodium in hemp chicken was studied by oral and intramuscular injection, and the plasma samples and tissue samples were taken by HPLC in different time points after the administration of ceftif sodium in the chicken. The pharmacokinetic characteristics of ceftif sodium in hemp chickens were examined and analyzed. The bioavailability of ceftif sodium in hemp chickens was analyzed. The pharmacokinetics of ceftif sodium in hemp chickens showed that ceftif sodium was given 20 m of ceftif sodium to the intramuscular injection. The prototype pharmacokinetic parameters of g/kg: the plasma peak concentration Cmax is (6.337 + 3.29) mu g/mL, the peak time Tmax is (0.25 + 0) h, the elimination half life t1/2 is (0.851 + 0.23) h, the elimination rate constant Ke is (0.883 + 0.32) H-1, AUC0-t is (5.338 + 2.85) mu g, H. 7) h, the clearance rate of CLtot was (72.950 + 28.53) m L. Min-1. Kg-1, the apparent distribution volume Vd was (5.250 + 2.20) L. Kg-1. intramuscular injection of ceftif sodium in its tissue did not detect ceftif sodium prototype drug. The pharmacokinetics of ceftif sodium 20 mg/kg in the oral chicken was studied: the oral ceftif sodium in hemp chicken was in its blood and group. No cefotaxime sodium was detected in the prototypes, indicating that cefuroxime sodium was not absorbed orally.

【学位授予单位】：山东农业大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：S859.7

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