肌注氟苯尼考在鸭疫里氏杆菌感染鸭体内的药动学特征

doi:10.3864/j.issn.0578-1752.2017.20.016

摘要/Abstract

摘要： 【目的】研究并比较肌注氟苯尼考在2周龄健康和鸭疫里氏杆菌感染鸭体内的药代动力学特征。【方法】240只鸭随机分为2组，各120只鸭，其中一组用鸭疫里氏杆菌腿部感染，分别以30 mg·kg^-1体重单剂量肌内注射氟苯尼考，采血点为给药前和给药后5、10、15、20、30、45 min和1、1.5、2、4、8、10、14 h。采用高效液相色谱法 (HPLC) 测定血浆氟苯尼考的浓度，采用紫外检测器检测，检测波长为223 nm，流动相为乙腈和水，其体积比为26和74 ，流速为1 mL·min^-1，色谱柱为Agilent C18 (4.6 mm×150 mm，5 μm)，进样量为20 μL。药动学分析软件 WinNonlin 5.2.1以非房室模型拟合处理血药浓度-时间数据，计算相关的药动学参数，并用统计学软件SPSS17.0对药动学参数进行t检验统计学分析。【结果】氟苯尼考在健康鸭体内的峰浓度(Cmax)为(22.88±3.11) μg·mL^-1，表观分布容积(Vd/F)为(2.39±0.81) L·kg^-1，体清除率(Cl_B/F)为(0.64±0.11) L·h^-1·kg^-1，消除半衰期(t_1/2_β)为 (2.57±0.51) h和药时曲线下面积(AUC)为(47.28±7.87) μg·mL^-1·h;氟苯尼考在感染鸭体内的峰浓度(C_max)为(19.77±1.82) μg·mL^-1，表观分布容积(Vd/F)为(2.44±0.46) L·kg^-1，体清除率(Cl_B/F)为(0.63±0.08) L·h^-1·kg^-1，消除半衰期(t_1/2_β)为(2.74±0.54) h和药时曲线下面积(AUC)为(48.11±6.62) μg·mL^-1·h 。统计分析氟苯尼考在健康鸭和感染鸭的药动学参数，结果表明，除了C_max差异显著(P<0.05)，其他参数差异均不显著(P>0.05)。【结论】两者的主要药动学参数相比较，感染鸭体内的C_max显著低于(P<0.05)健康鸭体内的C_max，其他参数无显著性差异。氟苯尼考以30 mg·kg^-1体重肌内注射在健康和感染鸭体内具有吸收迅速，峰浓度高,体内分布广泛，消除较快的特点。

关键词: 氟苯尼考, 鸭疫里氏杆菌, 药代动力学, 腿部感染, 鸭

Abstract: 【Objective】The pharmacokinetic properties of florfenicol were studied and compared in both healthy ducks and ducks infected with Riemerella anatipestifer after intramuscular administration.【Method】A total of 240 ducks were randomly divided into 2 equal groups of 120 ducks each, one groups infected with Riemerella anatipestifer in the thigh. The two groups were injected with florfenicol injection following intramuscular (i.m.) administration at a single dosage of 30 mg·kg^-1 body weight, respectively. Plasma samples were collected at 0, 5, 10, 15, 20, 30, 45 minutes and 1, 1.5, 2, 4, 6, 8, 10, and 14 hours after administration. The florfenicol concentration in plasma samples was analyzed using a high performance liquid chromatography (HPLC) method, with UV detector at 223 nm. The mobile phase (acetonitrile:water v/v 26/74) was delivered at a constant flow rate of 1mL·min^-1. The column used was an Agilent C₁₈ (4.6 mm×150 mm, 5 μm) column. A 20 μL aliquot of the reconstituted sample was injected onto the HPLC column. The drug concentration-time data were analyzed by non-compartmental analysis of pharmacokinetic software WinNonlin 5.2.1. Statistical analysis of pharmacokinetic parameters was carried out by statistical software SPSS17.0.【Result】The main pharmacokinetic parameters in healthy and infected ducks were as follows : the elimination half-life (t_1/2β) was (2.57±0.51) h and (2.74±0.54) h. the peak time (T_max) was (0.54±0.14) h and (0.55±0.18) h. the peak drug concentration (C_max) was (22.88±3.11) μg·mL^-1 and (19.77±1.82) μg·mL^-1; the apparent distribution volume (Vd/F) was (2.39±0.81) L·kg^-1 and (2.44±0.46) L·kg^-1; the total body clearance (Cl_B/F) was (0.64±0.11) L·h^-1·kg^-1 and (0.63±0.08) L·h^-1·kg^-1; the area under the drug concentration-time curve (AUC_last) was (47.28±7.87) μg·mL^-1·h and (48.11±6.62) μg·mL^-1·h, respectively. The pharmacokinetic parameters of florfenicol in healthy ducks and infected ducks were analyzed statistically. The results showed that there was no significant difference between the other parameters except C_max(P<0.05).【Conclusion】The peak drug concentration (C_max) in infected ducks was significantly lower (P<0.05) than that in healthy ducks. There was no significant difference between the other pharmacokinetic parameters. The characteristics of rapid absorption, high plasma concentration, wide distribution and faster elimination were showed following im florfenicol injection with a single dosage of 30 mg·kg^-1 body weight in healthy and infected ducks.

Key words: florfenico1, Riemerella anatipestifer, pharmacokinetics , thigh infection, ducks

梅献，万鹏，韩东东，裴鹏飞，曾庆林，李晓虹，曾振灵. 肌注氟苯尼考在鸭疫里氏杆菌感染鸭体内的药动学特征[J]. 中国农业科学, 2017, 50(20): 4021-4027.

MEI Xian, WAN Peng, HAN DongDong, PEI PengFei, ZENG QingLin, LI XiaoHong, ZENG ZhenLing. Pharmacokinetics of Florfenicol in Ducks Infected with Riemerella anatipestifer After Intramuscular Administration[J]. Scientia Agricultura Sinica, 2017, 50(20): 4021-4027.

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参考文献

[1] 郭玉璞, 陈德威, 范国雄, 刘瑞萍. 北京鸭小鸭传染性浆膜炎的调查研究. 畜牧兽医学报, 1982(2): 35-41.

GUO Y P, CHEN D W, FAN G X, LIU R P. Studys on infections serositis in white Beijing ducklings. Chinese Journal of Animal and Veterinary Sciences, 1982(2): 35-41. (in Chinese)

[2] 吴华, 李胜利, 侯百枝, 陈华, 胡功政. 鸭疫里氏杆菌病药物防治研究进展. 动物医学进展, 2007, 28(4):96-100.

WU H, LI S L, HOU B Z, CHEN H, HU G Z. Advance in medicines to combat Riemerella anatipestifer in duck. Progress in Veterinary Medicine, 2007, 28(4):96-100. (in Chinese)

[3] QIU Z Z, CAO C F, QU Y, LU Y, SUN M Z, ZHANG Y N, ZHONG J L, ZENG Z L. In vivo activity of cefquinome against Riemerella anatipestifer using the pericarditis model in the duck. Journal of Veterinary Pharmacology and Therapeutics,2016, 39(3): 299-304.

[4] 李先强. 氟苯尼考研究进展. 中国兽药杂志, 2016,11: 5-8.

LI X Q. Advance in the research of florfenicol. Chinese Journal of Veterinary Medicine, 2016, 11: 5-8. (in Chinese)

[5] YANG B, GAO J D, CAO X Y, WANG Q Y, SUN G Z, YANG J J. Lung microdialysis study of florfenicol in pigs after single intramuscular administration. Journal of Veterinary Pharmacology and Therapeutics, DOI:10.1111/jvp. 12387, 2017.

[6] SIDHU P, RASSOULI A, ILLAMBAS J, POTTER T, PELLIGAND L, RYCROFT A, LEES P. Pharmacokinetic-pharmacodynamic integration and modelling of florfenicol in calves. Journal of Veterinary Pharmacology and Therapeutics, 2014, 37(3): 231-242.

[7] KIM M H, GEBRU E, CHANG Z Q, CHOI J Y, HWANG M H, KANG E H, LIM J H, YUN H I, PARK S C. Comparative pharmacokinetics of tylosin or florfenicol after a single intramuscular administration at two different doses of Tylosin-Florfenicol combination in pigs. Journal of Veterinary Medical Science,2008, 70(1): 99-102.

[8] 谭元燕. 喹赛多对鸡沙门氏菌的PK-PD同步模型研究[D]. 武汉:华中农业大学, 2013.

TAN Y Y. Pharmacokinetic-pharmacodynamic modeling of cyadox against Salmonella pullorum in broiler [D]. Wuhan: Huazhong Agricultural University, 2013. (in Chinese)

[9] 王丽平，陆承平. 人工感染猪链球菌对小鼠肝脏药物代谢酶的抑制作用. 中国农业科学, 2009, 42(3): 1078-1083.

WANG L P, LU C P. Inhibition of hepatic drug-metabolizing enzymes in mice during Streptococcus suis type 2 infection. Scientia Agricultura Sinica, 2009, 42(3): 1078-1083. (in Chinese)

[10] 刘涤洁，冯淇辉，陈杖榴. 恩诺沙星在健康及实验性感染乳房炎奶山羊间的比较药动学. 中国农业科学, 2003, 36(9): 1100-1104.

LIU D J, FENG Q H, CHEN Z L. Study of comparative pharmacodynamics of enrofloxacin healthy and msatitis lactating goats experimentally infected with staphylococcus aureus. Scientia Agricultura Sinica, 2003, 36(9): 1100-1104. (in Chinese)

[11] CRAENE D B A, DEPREZ P, D'HAESE E, NELIS H J, BOSSCHE D W V, LEENHEER D A P. Pharmacokinetics of florfenicol in cerebrospinal fluid and plasma of calves. Antimicrob Agents Chemother, 1997, 41(9): 1991-1995.

[12] CHEN Y P, LEE S H, PAN M J, CHEN C L, SHIEN J H, CHANG T C, TSAI H J. Antimicrobial susceptibility of Riemerella anatipestifer isolated from ducks and geese and the Mutations of gyrase associated with quinolone resistance. Taiwan Veterinary Journal, 2012, 38(1): 7-18.

[13] 余金金, 温小鹏. 不同药物对鸭传染性浆膜炎的疗效观察. 江西畜牧兽医杂志, 2015(1): 8-9.

YU J J, WEN X P. Effection of different drugs on Riemerella anatipestifer. Jiangxi Journal of Animal Husbandry &Veterinary Medicine, 2015(1): 8-9. (in Chinese)

[14] LI Y F, ZHANG Y N, DING H Z, MEI X,LIU W, ZENG J X, ZENG Z L. In vitro susceptibility of four antimicrobials against Riemerella anatipestifer isolates: a comparison of minimum inhibitory concentrations and mutant prevention concentrations for ceftiofur, cefquinome, florfenicol, and tilmicosin. BMC Veterinary Research, 2016, 12(1): 250.

[15] 梁建明. 鸭疫里默氏菌病诊治与体会. 福建畜牧兽医, 2013(6): 61.

Liang J M. Diagnosis and experience of Riemerella anatipestifer. Fujian Journal of Animal Husbandry and Veterinary Medicine, 2013(6): 61. (in Chinese)

[16] SUN N, LIU J H, YANG F, LIN D C, LI G H, CHEN Z L, ZENG Z L. Molecular characterization of the antimicrobial resistance of Riemerella anatipestifer isolated from ducks. Veterinary Microbiology, 2012, 158(3-4): 376-383.

[17] WANG G Y, TU P, CHEN X, GUO Y G, JIANG S X. Effect of three polyether ionophores on pharmacokinetics of florfenicol in male broilers. Journal of Veterinary Pharmacology and Therapeutics, 2013, 36(5): 494-501.

[18] 安婷. 鸭疫里默氏杆菌在人工感染雏鸭体内的动态研究[D]. 雅安:四川农业大学, 2009.

AN T. Study on the dynamic variation in ducklings by artificially infected with Riemerella anatipestifer[D]. Ya'an: Sichuan Agricultural University, 2009. (in Chinese)

[19] 俞吉杰. 硫酸头孢喹肟对鸭传染性浆膜炎的药效药动学研究[D]. 南京:南京农业大学, 2008.

YU J J. Study on pharmacokinetics and pharmacodynamics of cefquinome in ducks infected by Riemerella anatipestifer[D]. Nanjing: Nanjing Agricultural University, 2008. (in Chinese)

[20] 段泽. RA分子流行病学调查和FQ-PCR检测人工感染RA在雏鸭体内的动态分布规律研究[D]. 雅安:四川农业大学, 2006.

DU Z. Molecular epidemiology survey of RA and researches of the dynamic distribution regular pattern in ducks artificially infected with RA[D] . Ya'an: Sichuan Agricultural University, 2006. (in Chinese)

[21] EL-BANNA H A. Pharmacokinetics of florfenicol in normal and Pasteurella-infected Muscovy ducks. British Poultry Science, 1998, 39(4): 492-496.

[22] 段新华, 杨帆. 静脉和肌内注射后氟苯尼考在麻鸭体内药动学的初步研究. 中国家禽, 2016(4): 19-22.

DUAN X H, YANG F. Pharmacokinetics of florfenicol after intravenous and intramuscular administration in partridge ducks. China Poultry, 2016(4): 19-22. (in Chinese)

[23] SHEN J Z, WU X A, HU D F, JIANG H Y. Pharmacokinetics of florfenicol in healthy and Escherichia coli-infected broiler chickens, Research in veterinary science,2002, 73(2): 137-140.

[24] ABD E A, GOUDAH A, ABO E K, EL-ZORBA H Y, SHIMODA M, ZHOU H H. Pharmacokinetics and bioavailability of florfenicol following intravenous, intramuscular and oral administrations in rabbits, Veterinary Research Communications,2004, 28(6): 515-524.

[25] BIRDANE Y O, BIRDANE F M. Pharmacokinetics of florfenicol following intravenous and intramuscular administration in dogs. Veterinarni Medicina,2015, 6:323-329.

[26] 董宏伟, 李忠杰, 吕淑荣, 刘万卉. 氟苯尼考注射液在大鼠体内代谢及生物利用度研究. 烟台大学学报(自然科学与工程版), 2014, 27(2): 122-125.

Dong H W, Li Z J, LÜ S R, Liu W H. Metabolism and bioavailability of florineicol injection in rats. Journal of Yantai University (Natural Science and Engineering Edition), 2014, 27(2):122-125. (in Chinese)

[27] 张旭, 薛克友, 王大菊, 赵芬琴，谢欣梅. 氟苯尼考在鸡体内的药动学及其体内抗菌后效应研究. 中国兽药杂志, 2008, 42(12): 39-42.

ZHANG X, XUE K Y, WANG D J, ZHAO F Q, XIE X M. Studies on pharmacokinetics of florfenicol in chicken and its post-antibiotic effects in vivo. Chinese Journal of Veterinary Drug, 2008, 42(12): 39-42. (in Chinese)

[28] 陈红伟, 李英伦. 单剂量氟苯尼考内服及肌注在家兔体内药代动力学研究. 中国兽医学报, 2008, 28(2): 166-169.

CHEN H W, LI Y L. The pharmacokinetics of florfenicol following a single oral and intramuscular administration to rabbits. Chinese Journal of Veterinary Science, 2008, 28(2):166-169.(in Chinese)

[29] 王加才. 氟苯尼考超微粉在肉鸡体内的药动学与药效学研究[D]. 南京:南京农业大学, 2006.

WANG J C. Study on pharmacokinetics and pharmacodymics of florfenicol ultrafine power in chicken[D]. Nanjing: Nanjing Agricultural University, 2006. (in Chinese)

[30] 李孝文，董伟，杨昆，陈小军，刘兆颖，孙志良. 氟苯尼考双混悬乳剂的体外药效学研究. 中国农业科学, 2011, 44(19): 4102-4109.

LI X W, DONG W, YANG K, CHEN X J, LIU Z Y, SUN Z L. Studies on pharmacodynamics in vitro of the florfenicol dual suspension emulsion. Scientia Agricultura Sinica. 2011, 44(19): 4102-4109. (in Chinese)