甲磺酸培氟沙星在麻鸡体内的药代动力学与组织分布的研究
发布时间：2018-07-17 22:14
【摘要】：背景:培氟沙星(Pefloxacin)为甲基-4-哌嗪喹诺酮类衍生物,是一种高效、低毒、广谱的抗菌药物,以吸收快、生物利用度好、组织药物浓度高、体内分布广、维持时间长为特点,临床应用主要用其甲磺酸盐。在体内对革兰氏阴性菌的抗菌活性与第三代头孢菌素及新氨基糖苷类相似,对衣原体、支原体、某些革兰氏阳性菌也有一定的抗菌作用。兽医临床上用来治疗常见细菌及支原体严重感染性疾病,已取得良好疗效,并能有效突破血脑屏障,与其他抗菌药物无交叉耐药性。近年来,甲磺酸培氟沙星在兽医临床上的应用越来越多。目前关于甲磺酸培氟沙星在麻鸡体内的药代动力学与组织分布的研究目前还是空白状态。药代动力学是定量研究药物在生物体内吸收、分布、代谢和排泄规律,并运用数学原理和方法阐述血药浓度随时间变化的规律的一门学科。因此,通过对甲磺酸培氟沙星在动物体内药动学的研究,制定科学合理的给药方式和剂量、给药时间,指导甲磺酸培氟沙星的临床用药具有重要意义。目前,甲磺酸培氟沙星的药代动力学研究主要集中在人、犬、山羊上,在家禽体内的药代动力学研究尚未见到有关报道。该实验通过对甲磺酸培氟沙星在麻鸡体内药代动力学的研究,阐明其在麻鸡体内的变化规律,为临床合理使用甲磺酸培氟沙星提供参考和借鉴。目的:为了可以更好地了解甲磺酸培氟沙星在健康麻鸡体内的吸收、分布、代谢、消除过程,建立了高效液相色谱法检测甲磺酸培氟沙星在麻鸡体内的药代动力学研究方法。通过对甲磺酸培氟沙星在麻鸡体内药物代谢动力学的研究,为甲磺酸培氟沙星在麻鸡病防治过程中的临床合理用药提供参考。方法:采用口服灌胃给药方式,在给药后不同的时间点进行麻鸡翅下静脉采血,运用高效液相色谱法进行检测甲磺酸培氟沙星的体内药物血药浓度变化,研究甲磺酸培氟沙星在麻鸡体内的药代动力学特点。试验采用甲醇进行液-液萃取的方法对血浆样品进行处理,选用恩诺沙星作为内标;高效液相色谱仪为日本岛津LC-10A;色谱柱为shimadzu ODS-C18柱(250×4.6mm,5μm),日本岛津公司;检测波长为276 nm;流动相:0.025 moL/L磷酸溶液(三乙胺调pH 3.1±0.1)-乙腈(80:20,V/V),流速:1 mL/min,进样量是20μL的色谱条件进行检测。甲磺酸培氟沙星和恩诺沙星的保留时间分别为6.1 min和8.0min。结果:药代动力学研究发现,对麻鸡经口给药甲磺酸培氟沙星20 mg/kg的药代动力学参数:血浆达峰浓度Cmax为(6886.7±444.6)ng/m L,达峰时间Tmax为2 h,消除半衰期t1/2为(7.03±0.17)h,消除速率常数Ke为0.10 h-1,AUC0-t为(64333.4±2309.0)ng·h·mL-1,AUC0→∞为(66507.3±2428.7)ng·h·mL-1,平均滞留时间MRT为(7.67±0.18)h,清除率CLtot为(5.0±0.19)mL·min-1·kg-1,表观分布容积Vz为(3.05±0.11)L·kg-1。组织分布研究结果发现,麻鸡口服甲磺酸培氟沙星20 mg/kg后,在肝脏内的药物浓度最高,达峰浓度Cmax为(16800.0±1914.4)ng/m L,达峰时间Tmax为1 h,消除半衰期t1/2为(33.70±8.80)h,其次为肾脏,达峰浓度Cmax为(15980.0±5856.4)ng/mL,达峰时间Tmax为1 h,消除半衰期t1/2为(17.30±3.9)h。在肺脏、腿肌、脑、骨髓、胰腺等均能检测到甲磺酸培氟沙星,含量很低,但是持续时间很长,容易造成蓄积。胸肌在检测的过程中,未检测到任何浓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.
【学位授予单位】：山东农业大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：S859.79
本文编号：2131092
[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.
【学位授予单位】：山东农业大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：S859.79
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