【摘要】：背景:培氟沙星(Pefloxacin)為甲基-4-哌嗪喹諾酮類衍生物,是一種高效、低毒、廣譜的抗菌藥物,以吸收快、生物利用度好、組織藥物濃度高、體內(nèi)分布廣、維持時間長為特點,臨床應用主要用其甲磺酸鹽。在體內(nèi)對革蘭氏陰性菌的抗菌活性與第三代頭孢菌素及新氨基糖苷類相似,對衣原體、支原體、某些革蘭氏陽性菌也有一定的抗菌作用。獸醫(yī)臨床上用來治療常見細菌及支原體嚴重感染性疾病,已取得良好療效,并能有效突破血腦屏障,與其他抗菌藥物無交叉耐藥性。近年來,甲磺酸培氟沙星在獸醫(yī)臨床上的應用越來越多。目前關于甲磺酸培氟沙星在麻雞體內(nèi)的藥代動力學與組織分布的研究目前還是空白狀態(tài)。藥代動力學是定量研究藥物在生物體內(nèi)吸收、分布、代謝和排泄規(guī)律,并運用數(shù)學原理和方法闡述血藥濃度隨時間變化的規(guī)律的一門學科。因此,通過對甲磺酸培氟沙星在動物體內(nèi)藥動學的研究,制定科學合理的給藥方式和劑量、給藥時間,指導甲磺酸培氟沙星的臨床用藥具有重要意義。目前,甲磺酸培氟沙星的藥代動力學研究主要集中在人、犬、山羊上,在家禽體內(nèi)的藥代動力學研究尚未見到有關報道。該實驗通過對甲磺酸培氟沙星在麻雞體內(nèi)藥代動力學的研究,闡明其在麻雞體內(nèi)的變化規(guī)律,為臨床合理使用甲磺酸培氟沙星提供參考和借鑒。目的:為了可以更好地了解甲磺酸培氟沙星在健康麻雞體內(nèi)的吸收、分布、代謝、消除過程,建立了高效液相色譜法檢測甲磺酸培氟沙星在麻雞體內(nèi)的藥代動力學研究方法。通過對甲磺酸培氟沙星在麻雞體內(nèi)藥物代謝動力學的研究,為甲磺酸培氟沙星在麻雞病防治過程中的臨床合理用藥提供參考。方法:采用口服灌胃給藥方式,在給藥后不同的時間點進行麻雞翅下靜脈采血,運用高效液相色譜法進行檢測甲磺酸培氟沙星的體內(nèi)藥物血藥濃度變化,研究甲磺酸培氟沙星在麻雞體內(nèi)的藥代動力學特點。試驗采用甲醇進行液-液萃取的方法對血漿樣品進行處理,選用恩諾沙星作為內(nèi)標;高效液相色譜儀為日本島津LC-10A;色譜柱為shimadzu ODS-C18柱(250×4.6mm,5μm),日本島津公司;檢測波長為276 nm;流動相:0.025 moL/L磷酸溶液(三乙胺調(diào)pH 3.1±0.1)-乙腈(80:20,V/V),流速:1 mL/min,進樣量是20μL的色譜條件進行檢測。甲磺酸培氟沙星和恩諾沙星的保留時間分別為6.1 min和8.0min。結果:藥代動力學研究發(fā)現(xiàn),對麻雞經(jīng)口給藥甲磺酸培氟沙星20 mg/kg的藥代動力學參數(shù):血漿達峰濃度Cmax為(6886.7±444.6)ng/m L,達峰時間Tmax為2 h,消除半衰期t1/2為(7.03±0.17)h,消除速率常數(shù)Ke為0.10 h-1,AUC0-t為(64333.4±2309.0)ng·h·mL-1,AUC0→∞為(66507.3±2428.7)ng·h·mL-1,平均滯留時間MRT為(7.67±0.18)h,清除率CLtot為(5.0±0.19)mL·min-1·kg-1,表觀分布容積Vz為(3.05±0.11)L·kg-1。組織分布研究結果發(fā)現(xiàn),麻雞口服甲磺酸培氟沙星20 mg/kg后,在肝臟內(nèi)的藥物濃度最高,達峰濃度Cmax為(16800.0±1914.4)ng/m L,達峰時間Tmax為1 h,消除半衰期t1/2為(33.70±8.80)h,其次為腎臟,達峰濃度Cmax為(15980.0±5856.4)ng/mL,達峰時間Tmax為1 h,消除半衰期t1/2為(17.30±3.9)h。在肺臟、腿肌、腦、骨髓、胰腺等均能檢測到甲磺酸培氟沙星,含量很低,但是持續(xù)時間很長,容易造成蓄積。胸肌在檢測的過程中,未檢測到任何濃度的甲磺酸培氟沙星。
[Abstract]:Background: Pefloxacin (Pefloxacin) is a methyl -4- piperazine quinolone derivative. It is a highly effective, low toxic and broad-spectrum antibacterial agent. It is characterized by fast absorption, good bioavailability, high tissue drug concentration, wide distribution in the body and long maintenance time. Its clinical application mainly uses its sulfonates. The three generation cephalosporins and new aminoglycosides are similar to the chlamydia, mycoplasma and some gram-positive bacteria. The veterinary clinic has been used to treat common bacteria and Mycoplasma serious infectious diseases. It has achieved good curative effect, and can effectively break through the blood brain barrier and have no cross resistance with other antibiotics. There are more and more clinical applications of pefloxacin mesylate in veterinary clinic. At present, the study on the pharmacokinetics and tissue distribution of pefloxacin mesylate in hemp chicken is still blank. Pharmacokinetics is a quantitative study of the laws of absorption, distribution, metabolism and excretion of drugs in organisms, and expounds the principles and methods of Mathematics. The pharmacokinetics of pefloxacin mesylate is of great significance in the study of the pharmacokinetics of pefloxacin mesylate in animals, and it is of great significance to guide the clinical medication of pefloxacin mesylate. The study on pharmacokinetics of people, dogs and goats in poultry has not been reported. The experimental study on the pharmacokinetics of pefloxacin mesylate in hemp chickens, to clarify its changes in the body of the chicken, provide reference and reference for the rational use of pefloxacin mesylate. To understand the absorption, distribution, metabolism and elimination process of pefloxacin mesylate in healthy hemp chicken, a high performance liquid chromatography method was established for the study of the pharmacokinetics of pefloxacin mesylate in hemp chicken. To provide reference for the rational use of drugs in the prevention and control of chicken disease. Methods: oral administration of oral administration by oral administration of the stomach was carried out at different time points after the administration. The blood concentration of pefloxacin mesylate in vivo was detected by high performance liquid chromatography. Dynamic characteristics. The plasma samples were treated with methanol and liquid liquid extraction, and enrofloxacin was selected as internal standard; the HPLC chromatograph was Japanese SHIMADZU LC-10A; the chromatographic column was Shimadzu ODS-C18 column (250 x 4.6mm, 5 mu m), Shimadzu Corporation; detection wavelength was 276 nm; mobile phase: 0.025 moL/L phosphoric acid solution (three ethylamine). PH 3.1 + 0.1) - acetonitrile (80:20, V/V), flow rate: 1 mL/min, the sample volume was 20 mu L. The retention time of pefloxacin mesylate and enrofloxacin was 6.1 min and 8.0min., respectively. Pharmacokinetics study found that the pharmacokinetic parameters of perflofloxacin 20 mg/kg in the oral administration of hemp chicken: plasma peak concentration The degree Cmax is (6886.7 + 444.6) ng/m L, the peak time Tmax is 2 h, the elimination half life t1/2 is (7.03 + 0.17) h, the elimination rate constant Ke is 0.10 H-1, AUC0-t is (64333.4 + 2309) ng, H. The volume Vz was (3.05 + 0.11) L / kg-1. tissue distribution, and it was found that the drug concentration in the liver was the highest after oral administration of pefloxacin mesilate 20 mg/kg, the peak concentration Cmax was (16800 + 1914.4) ng/m L, the peak time Tmax was 1 h, the half-life t1/2 was (33.70 + 8.80) h, followed by the kidney, and the peak concentration Cmax was (15980 + 5856.4). ML, the peak time Tmax is 1 h, the half-life t1/2 is (17.30 + 3.9) H. in the lung, the leg muscles, the brain, the bone marrow, the pancreas, etc. The pefloxacin mesylate can be detected, the content is very low, but the duration is very long and easy to accumulate. No pefloxacin mesylate is detected during the detection of the chest muscle.
【學位授予單位】：山東農(nóng)業(yè)大學
【學位級別】：碩士
【學位授予年份】：2015
【分類號】：S859.79

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