恩诺沙星灌注液在健康母猪体内的药代动力学研究

doi:10.11843/j.issn.0366-6964.2016.07.024

摘要/Abstract

摘要：

旨在考察恩诺沙星灌注液与恩诺沙星普通注射液在母猪体内的药代动力学特征。作者选用16头健康长白×大白二元杂交成年母猪，随机分成2组，每组8头，分别进行单剂量耳缘静脉注射恩诺沙星普通注射液（2.5 mg•kg^-1）和子宫灌注恩诺沙星灌注液（50 mL•头^-1），反相高效液相色谱法（RP-HPLC）测定母猪血浆中恩诺沙星及其代谢产物环丙沙星含量，运用药动学软件Winnonlin 5.2.1非房室模型分析并计算出相关药动学参数。结果显示，静脉注射恩诺沙星普通注射液后，其主要药动学参数如下：t _1/2 （21.71±1.66）h，Vd（1.89±0.33）L•kg^-1，Cl（60.18±8.92）mL•h^-1•kg^-1，AUC_0-t（39.94±5.75）mg•h•L^-1，AUC_0-∞ （42.32±6.03）mg•h•L^-1。母猪子宫灌注恩诺沙星灌注液后，其主要药动学参数分别如下：t _1/2（28.55±2.31）h，T_max （3.19±1.46）h，C_max（1.61±0.20）mg•L^-1，AUC_0-t （49.06±5.18）mg•h•L^-1，AUC _0-∞（53.55±5.84）mg•h•L^-1，F为63.15%。所有样品中均未检测出环丙沙星。结果表明，恩诺沙星灌注液可经子宫灌注吸收进入母猪体内，并且在母猪体内分布广泛，消除缓慢，生物利用度较高，临床用药时应考虑局部给药对机体的全身性影响。

Abstract:

This study was designed to compare the pharmacokinetic parameters of enrofloxacin following intravenous and intrauterine administrations to investigate their bioavailability in sows.16 cross-bred (Landrace×Yorkshire) healthy，adult，non-lactating sows，were used.The sows were randomly divided into two groups with eight animals each.The sows of first group were administered with enrofloxacin injection by intravenous route，at a single dose of 2.5 mg•kg^-1；whereas those of second group were administered with enrofloxacin uterine perfusate by intrauterine administration at a single dose of 50 mL per sow.Enrofloxacin concentrations were determined by reverse phase-high performance liquid chromatography (RP-HPLC) with fluorescence detection.A non-compartmental analysis of drug plasma concentration vs.time profiles was performed with pharmacokinetic modeling using Winnonlin software.Following intravenous administration，the main pharmacokinetic parameters were as follows：t _1/2（21.71±1.66）h，Vd（1.89±0.33）L•kg^-1， Cl（60.18±8.92）mL•h^-1•kg^-1，AUC_0-t（39.94±5.75）mg•h•L^-1，AUC_0-∞（42.32±6.03）mg•h•L^-1.The absorption of enrofloxacin was rapid and well absorbed after intrauterine administration，with t _1/2 of （28.55±2.31）h，T_maxof （3.19±1.46）h，C_max of （1.61±0.20）mg•L^-1，AUC_0-t of （49.06±5.18）mg•h•L^-1，AUC _0-∞（53.55±5.84）mg•h•L^-1.The absolute bioavailability (F) was 63.15%.Concentrations of the active metabolite ciprofloxacin were not detected in any samples.The results showed that the sows can absorb enrofloxacin well by way of intrauterine administration，with slow elimination and high bioavailability.And the effect on body after intrauterine administration should be considered.

中图分类号:

S859.7

冯庭松，黄显会，曾松情，郜进，谢顺，刘宇. 恩诺沙星灌注液在健康母猪体内的药代动力学研究[J]. 畜牧兽医学报, 2016, 47(7): 1488-1494.

FENG Ting-song，HUANG Xian-hui，ZENG Song-qing，GAO Jin，XIE Shun，LIU Yu.

Pharmacokinetics of Enrofloxacin Perfusate in Healthy Sows[J]. ACTA VETERINARIA ET ZOOTECHNICA SINICA, 2016, 47(7): 1488-1494.

0
/ / 推荐

导出引用管理器 EndNote|Reference Manager|ProCite|BibTeX|RefWorks

链接本文: https://www.xmsyxb.com/CN/10.11843/j.issn.0366-6964.2016.07.024

https://www.xmsyxb.com/CN/Y2016/V47/I7/1488

参考文献

［1］叶健毅，赵学峰，兰邹然，等.规模化猪场母猪子宫内膜炎致病菌的分离鉴定［J］.畜牧兽医杂志，2011，30(1)：5-7.
YE J Y，ZHAO X F，LAN Z R，et al.Pathogenic bacteria isolation and identification of sow endometritis in scale breeding pig［J］.Journal of Animal Science and Veterinary Medicine，2011，30(1)：5-7.(in Chinese)
［2］李想.宫炎净灌注液对母猪子宫内膜炎的临床疗效观察［J］.中国猪业，2015(1)：51-54.
LI X.Treatment effect of Gongyanjing perfusate on endometritis in sows［J］.China Swine Industry，2015(1)：51-54.(in Chinese)
［3］WOLFSON J S，HOOPER D C.The fluoroquinolones：structures，mechanisms of action and resistance，and spectra of activity in vitro［J］.Antimicrob Agents Chenother，1985，28(4)：581-586.
［4］VANCUTSEM P M，BABISH J G，SCHWARK W S.The fluoroquinolone antimicrobials：structure，antimicrobial activity，pharmacokinetics，clinical use in domestic animals and toxicity［J］.Cornell Vet，1990，80(2)：173-186.
［5］NIELSEN P，GYRD-HANSEN N.Bioavailability of enrofloxacin after oral administration to fed and fasted pigs［J］.Pharmacol Toxicol，1997，80(5)：246-250.
［6］PIJPERS A，HEINEN E.Enrofloxacin pharmacokinetics after intravenous and intramuscular administration in pigs［J］.J Vet Pharmacol Ther，1997，20(1)：13.
［7］GORE S R，HARMS C A，KUKANICH B，et al.Enrofloxacin pharmacokinetics in the European cuttlefish，Sepia officinalis，after a single i.v.injection and bath administration［J］.J Vet Pharmacol Ther，2005，28(5)：433-439.
［8］PEYROU M，BOUSQUET-MELOU A，LAROUTE V，et al.Enrofloxacin and marbofloxacin in horses：comparison of pharmacokinetic parameters，use of urinary and metabolite data to estimate first-pass effect and absorbed fraction［J］.J Vet Pharmacol Ther，2006，29(5)：337-344.
［9］HOWARD J T，BAYNES R E，BROOKS J D，et al.The effect of breed and sex on sulfamethazine，enrofloxacin，fenbendazole and flunixin meglumine pharmacokinetic parameters in swine［J］. J Vet Pharmacol Ther，2014，37(6)：531-541.
［10］LASHEV L D，DIMITROVA D J，MILANOVA A，et al.Pharmacokinetics of enrofloxacin and marbofloxacin in Japanese quails and common pheasants［J］.Br Poult Sci，2015，56(2)：255-261.
［11］FUMUSO E，CHECURA C，LOSINNO L，et al.Endometrial tissue concentrations of enrofloxacin after intrauterine administration to mares［J］.Vet Res Commun，2002，26(5)：371-380.
［12］PETRACCA K，RIOND J L，GRASER T，et al.Pharmacokinetics of the gyrase inhibitor marbofloxacin：influence of pregnancy and lactation in sows［J］Zentralbl Veterinarmed A，1993，40(1)：73-79.
［13］DING H Z，YANG G X，HUANG X H，et al.Pharmacokinetics of difloxacin in pigs and broilers following intravenous，intramuscular，and oral single-dose applications［J］.J Vet Pharmacol Ther，2008，31(3)：200-204.
［14］李云峰，曾振灵，陈杖榴，等.麻保沙星(marbofloxacin)在猪体内的药物动力学［J］.中国兽医学报，2004，24(2)：177-180.
LI Y F，ZENG Z L，CHEN Z L，et al.Pharmacokinetics of marbofloxacin in pigs［J］.Chinese Journal of Veterinary，2004，24(2)：177-180.(in Chinese)
［15］MANN D D，FRAME G M.Pharmacokinetic study of danofloxacin in cattle and swine［J］.Am J Vet Res，1992，53(6)：1022-1026.
［16］曾振灵，丁焕中，黄显会，等.二氟沙星在猪体内的药物动力学及生物利用度研究［J］.中国农业科学，2003，36(7)：846-850.
ZENG Z L，DING H Z，HUANG X H，et al.Pharmacokinetics and bioavailability of difloxacin in pigs［J］.Scientia Agricultura Sinica，2003，36(7)：846-850.(in Chinese)
［17］曾振灵，冯淇辉.恩诺沙星在猪体内的生物利用度及药物动力学研究［J］.中国兽医学报，1996，16(6)：607-613.
ZENG Z L，FENG Q H.Pharmacokinetics and bioavailability of enrofloxacin in pigs［J］.Chinese Journal of Veterinary Science，1996，16(6)：607-613.(in Chinese)
［18］DE WINTER P J J，VERDONCK M，DE KRUIF A，et al.Bacterial endometritis and vaginal discharge in the sow：prevalence of different bacterial species and experimental reproduction of the syndrome［J］. Anim Reprod Sci，1995，37(3-4)：325-335.
［19］DE WINTER P J J，VERDONCK M，DE KRUIF A，et al.Endometritis and vaginal discharge in the sow［J］.Anim Reprod Sci，1992，28(1-4)：51-58.
［20］SCHEER M.Enrofloxacin (Baytril) microbiological profile and pharmacokinetics in several species of animal//Veterinary Pharmacology，Toxicology and Therapy in Food Producing Animals［M］.Simon F，eds.Budapest：University of Veterinary Science-Unipharma Co Ltd，1990：15-20.
［21］MUELLER M，DE LA PEA A，DERENDORF H.Issues in pharmacokinetics and pharmacodynamics of anti-infective agents：kill curves versus MIC［J］.Antimicrob Agents Chemother，2004，48(2)：369-377.
［22］DALHOFF A，WEUTA H.Penetration of ciprofloxacin into gynecologic tissues［J］.Am J Med，1987，82(4A)：133-138.

[1]	周文惠, 包红霞, 王俊豪, 黄远玲, 王文惠, 郝海红. 甘草查尔酮A与三种抗生素联用对产气荚膜梭菌感染小鼠的治疗作用[J]. 畜牧兽医学报, 2024, 55(1): 334-345.
[2]	范锦全, 张宇航, 唐午阳, 赵欣宇, 李丕顺, 郑晓峰. 地西他滨对猪圆环病毒2型的体外抑制作用[J]. 畜牧兽医学报, 2023, 54(12): 5134-5142.
[3]	梁雾滢, 刘镇, 曾玉淇, 吕俊瑾, 莫睿文, 远立国. 1-甲基海因对慢性疼痛大鼠钠离子通道蛋白Nav1.8的干预作用[J]. 畜牧兽医学报, 2023, 54(12): 5312-5317.
[4]	单强, 王雪, 朱要宏, 王九峰. 鼠李糖乳杆菌抗炎机制及其在防治家畜疾病中的应用前景[J]. 畜牧兽医学报, 2023, 54(11): 4537-4550.
[5]	武周慧, 王瑜, 杜衡, 王之文, 肖爽, 武金亮, 王真. 替拉扎明对多重耐药沙门菌抗菌增敏活性分析[J]. 畜牧兽医学报, 2023, 54(10): 4362-4371.
[6]	孙盼盼, 曹志刚, 凌小雅, 孙娜, 孙耀贵, 李宏全. 苦参碱联合不同抗生素抗炎作用比较研究[J]. 畜牧兽医学报, 2023, 54(10): 4411-4421.
[7]	王志霞, 白莉霞, 秦哲, 刘希望, 杨亚军, 李世宏, 葛闻博, 李剑勇. 阿司匹林丁香酚酯颗粒剂有关物质检测方法的建立与验证[J]. 畜牧兽医学报, 2023, 54(8): 3500-3509.
[8]	王芮杰, 洪志楷, 董英娇, 陈瑶, 王晋宇, 王冠华. 基于UPLC-Q-TOF-MS/MS代谢组学研究土霉素和穿心莲内酯对鸡代谢的影响[J]. 畜牧兽医学报, 2023, 54(7): 3078-3090.
[9]	张潇, 李丹丹, 田红利, 欧春敏, 杨龙, 欧阳五庆, 郑寅. 侧柏叶抗红色毛癣菌主要活性成分α-蒎烯以ERG-3为靶点发挥抗真菌作用[J]. 畜牧兽医学报, 2023, 54(4): 1690-1702.
[10]	林梦娟, 高沙沙, 赵星辰, 仲宇欣, 吴俊, 张军忍, 郭大伟. 常山酮抗原虫作用研究进展[J]. 畜牧兽医学报, 2023, 54(3): 924-933.
[11]	陈洋, 王悦力, 陈诗奇, 李楠鑫, 张伟, 舒刚, 徐傅能, 李昊欢, 林居纯, 符华林. 基于寡肽转运蛋白的氟苯尼考肠吸收特性研究[J]. 畜牧兽医学报, 2023, 54(3): 1240-1248.
[12]	杨艳北, 许晶, 刘婉萍, 陶艾妮, 冯育林, 孙勇, 王闯, 刘建. 低浓度阿奇霉素对猪链球菌2型蛋白表达、荚膜多糖与药物敏感性的影响[J]. 畜牧兽医学报, 2023, 54(2): 757-765.
[13]	洪冕, 黄佳敏, 陈冬梅, 谢书宇. 纳米技术抗耐药菌的研究进展[J]. 畜牧兽医学报, 2022, 53(11): 3731-3736.
[14]	刘旭, 潘寅川, 杨亚军, 刘希望, 马宁, 李剑勇. 阿司匹林丁香酚酯对体外脂多糖诱导小鼠巨噬细胞炎症反应的抑制效应[J]. 畜牧兽医学报, 2022, 53(11): 4048-4057.
[15]	黄颖然, 叶欣晴, 刘娟, 于洋. 细菌附属敏感性：优化药物治疗的新思路[J]. 畜牧兽医学报, 2022, 53(10): 3316-3325.