42卷 星及其代谢产物环丙沙星在动物体内的共同作用是本 residues in the porcine tissues. Chinese Joumal of veterinary 药的最大特点,也是此药效果优于其他同类药物而在 Medicine, 2005, 39(2): 6-9.(in Chinese 动物中广泛应用的一个重要原因。按统计矩计算,在4]刘涤洁,冯淇辉,陈杖榴.恩诺沙星及其代谢产物在奶山羊的药动 健康区的环丙沙星的消除速率常数与患病区的环丙沙 学及乳中药物浓度.中国兽药杂志,2003,39(2)41-44 星的消除速率常数相比,由0.42降到028,患病区的 Liu d J, Feng Q H, Chen Z L Pharmacokinetics of enrofloxacin and 环丙沙星的AUC增加,这可从侧面说明乳房炎奶牛 its metabolites and their concentration in the milk of healthy lactating 乳房内灌注恩诺沙星可以改变药物的代谢和排泄,使 goats. Chinese Journal of veterinary Medicine, 2003, 39(2): 41-44 其代谢物的代谢率下降,消除速率常数降低。代谢物 环丙沙星的消除半衰期较母药长,平均为(167020)15 Cinquin A L, Roberti P, Giannetti L,, Longo f, Draisci R, Fagiolo A h,平均滞留时间(MRT)亦长。 Brizioli nR. Determination of enrofloxacin and its metabolite 3.3临床弃乳期的确定 ciprofloxacin in goat milk by high-performance liquid 1%恩诺沙星乳房灌注治疗奶牛临床型乳房炎,其 chromatography with diode-array detection: optimization and 废弃期实际上应是环丙沙星消除到最高残留限量 validation. Journal of chromatography 4, 2003, 987: 221-226 (MRL)以下的时间。据欧盟规定恩诺沙星在动物食6 Hoof v, Wasch K D. Kerman L, Reybroeck W, Poelmans s, 品组织中残留量MRL为003μgm,根据本试验测 Noppe H, Brabander H D. Validation of a liquid chromatography 得的环丙沙星在乳中的残留浓度低于最高残留限量 tandem mass spectrometric method for the quantification of eight (MRL)003ugm的时间为24h,因此在此时间 quinolones in bovine muscle, milk and aquacultured products. 加上1~2d的休药期,推算恩诺沙星在牛奶中的弃乳 Analytica Chimica Acta, 2005, 529: 265-272. 期不小于3d。该结果可为有关部门制定关于1%恩诺[7] Idowu R, Pegging J C. Simple, rapid determination of enrofloxacin 沙星单剂量乳房灌注治疗奶牛临床型乳房炎的休药期 and ciprofloxacin in bovine milk and plasma by high-performance 提供参考 uid chromatography with fluorescence detection. Journal of 结论 Pharmaceutical and Biomedical Analsis. 2004. 35: 143-153 [8] Marazuela M D, Moreno-Bondi M C Multiresidue determination of 恩诺沙星吸收较迅速,代谢较快、清除较快,表 恩诺沙星与环丙沙星在乳中不会形成残留 fluorescence and ultraviolet absorbance detection. Journal oj Chromatography 4, 2004, 1034: 25-32 References 19]曾彬,张晓菊.奶牛乳房炎的研究进展.养殖与饲料,2007(1 韩建春,佟恒敏,郭世宁,李继昌.恩诺沙星在奶牛血液和乳中药 物浓度的监测.动物保健品,2004,(5)58-60 Zeng B, Zhang X J. The study of bovine mastitis. Animals Breeding Han J C. Tong H M. Guo SN. Li J C. Monitor of the concentration of and Feed, 2007, (1): 31-36.(in Chinese enrofloxacin in the blood and milk in cows. Animal science and[o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 Veterinary Medicine, 2004, (5): 58-60.(in Chinese) 山羊间的比较药动学.中国农业科学,2003,36(91100-1104 2]沈永聪,师志海,张怀翼,梅承,沈祥广,李守军.恩诺沙星乳房 Liu D J, Feng Q H, Chen Z L Study of comparative pharmacokinetics 灌注后在牛奶中的残留检测.中国兽医杂志,2006,42(11)48-50 Shen Y C, Shi Z H, Zhang H Y, Mei C, Shen X G, Li s J. Determination of enrofloxacin in residues in cows milk by Smca,2003,36(9):1100-1104.( in Chinese) intramammary infusion. Chinese Journal of Veterinary Medicine,1夏文江,成章瑞 MCPKP:一种微机用药物动力学专用程序.中国 2006,42(11):48-50. n Chinese) 兽医科技,1986,(4)57-60. 3]仲锋,郭筱华,黄齐颐,董琳琳,刘艳华,周昭明,曾勇,金秀 Xia w J, Cheng Z R. MCPKP-a tiny pharmacokinetics analysis 娥,卢芳,韩直渊.恩诺沙星在猪组织中残留消除规律的研究 program. Chinese Journal of veterinary Science and Technolog 中国兽药杂志,2005,3902)6-9 986,(4):57-60.( in Chinese) Zhong F, Guo XH, Huang QY, Dong LL, Liu F, Zhou z M, zeng[2]宋振玉,刘耕陶.当代药理学.北京:中国协和医科大学及北京医 Y, Jin X E, Lu F, Han Z Y. Studies on the depletion of enrofloxacin in 科大学联合出版社,1994:107-122. o1994-2009chinaAcademicJournalElectronicpUblishingHouse.Allrightsreservedhttp://www.cnki.net316 中 国 农 业 科 学 42 卷 星及其代谢产物环丙沙星在动物体内的共同作用是本 药的最大特点，也是此药效果优于其他同类药物而在 动物中广泛应用的一个重要原因。按统计矩计算，在 健康区的环丙沙星的消除速率常数与患病区的环丙沙 星的消除速率常数相比，由 0.42 降到 0.28，患病区的 环丙沙星的 AUC 增加，这可从侧面说明乳房炎奶牛 乳房内灌注恩诺沙星可以改变药物的代谢和排泄，使 其代谢物的代谢率下降，消除速率常数降低。代谢物 环丙沙星的消除半衰期较母药长，平均为（1.67±0.20） h，平均滞留时间（MRT）亦长。 3.3 临床弃乳期的确定 1%恩诺沙星乳房灌注治疗奶牛临床型乳房炎，其 废弃期实际上应是环丙沙星消除到最高残留限量 （MRL）以下的时间。据欧盟规定恩诺沙星在动物食 品组织中残留量 MRL 为 0.03 µg·ml-1，根据本试验测 得的环丙沙星在乳中的残留浓度低于最高残留限量 （MRL）0.03 µg·ml-1的时间为 24 h，因此在此时间上 加上 1～2 d 的休药期，推算恩诺沙星在牛奶中的弃乳 期不小于 3 d。该结果可为有关部门制定关于 1%恩诺 沙星单剂量乳房灌注治疗奶牛临床型乳房炎的休药期 提供参考。 4 结论 恩诺沙星吸收较迅速，代谢较快、清除较快，表 明恩诺沙星与环丙沙星在乳中不会形成残留。 References [1] 韩建春, 佟恒敏, 郭世宁, 李继昌. 恩诺沙星在奶牛血液和乳中药 物浓度的监测. 动物保健品, 2004, (5): 58-60. Han J C, Tong H M, Guo S N, Li J C. Monitor of the concentration of enrofloxacin in the blood and milk in cows. Animal Science and Veterinary Medicine, 2004, (5): 58-60. (in Chinese) [2] 沈永聪, 师志海, 张怀翼, 梅 承, 沈祥广, 李守军. 恩诺沙星乳房 灌注后在牛奶中的残留检测. 中国兽医杂志, 2006, 42(11): 48-50. Shen Y C, Shi Z H, Zhang H Y, Mei C, Shen X G, Li S J. Determination of enrofloxacin in residues in cows milk by intramammary infusion. Chinese Journal of Veterinary Medicine, 2006, 42(11): 48-50. (in Chinese) [3] 仲 锋, 郭筱华, 黄齐颐, 董琳琳, 刘艳华, 周昭明, 曾 勇, 金秀 娥, 卢 芳, 韩直渊. 恩诺沙星在猪组织中残留消除规律的研究. 中国兽药杂志, 2005, 39(2): 6-9. Zhong F, Guo X H, Huang Q Y, Dong L L, Liu Y H, Zhou Z M, Zeng Y, Jin X E, Lu F, Han Z Y. Studies on the depletion of enrofloxacin in residues in the porcine tissues. Chinese Journal of Veterinary Medicine, 2005, 39(2): 6-9. (in Chinese) [4] 刘涤洁, 冯淇辉, 陈杖榴. 恩诺沙星及其代谢产物在奶山羊的药动 学及乳中药物浓度. 中国兽药杂志, 2003, 39(2): 41-44. Liu D J, Feng Q H, Chen Z L. Pharmacokinetics of enrofloxacin and its metabolites and their concentration in the milk of healthy lactating goats. Chinese Journal of Veterinary Medicine, 2003, 39(2): 41-44. (in Chinese) [5] Cinquina A L, Roberti P, Giannetti L, Longo F, Draisci R, Fagiolo A, Brizioli N R. Determination of enrofloxacin and its metabolite ciprofloxacin in goat milk by high-performance liquid chromatography with diode-array detection: optimization and validation. Journal of Chromatography A, 2003, 987: 221-226. [6] Hoof N V, Wasch K D, Okerman L, Reybroeck W, Poelmans S, Noppe H, Brabander H D. Validation of a liquid chromatography￾tandem mass spectrometric method for the quantification of eight quinolones in bovine muscle, milk and aquacultured products. Analytica Chimica Acta, 2005, 529: 265-272. [7] Idowu O R, Peggins J O. Simple, rapid determination of enrofloxacin and ciprofloxacin in bovine milk and plasma by high-performance liquid chromatography with fluorescence detection. Journal of Pharmaceutical and Biomedical Analysis, 2004, 35: 143-153. [8] Marazuela M D, Moreno-Bondi M C. Multiresidue determination of fluoroquinolones in milk by column liquid chromatography with fluorescence and ultraviolet absorbance detection. Journal of Chromatography A, 2004, 1034: 25-32. [9] 曾 彬, 张晓菊. 奶牛乳房炎的研究进展. 养殖与饲料, 2007, (1): 31-36. Zeng B, Zhang X J. The study of bovine mastitis. Animals Breeding and Feed, 2007, (1): 31-36. (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 pharmacokinetics of enrofloxacin in healthy and mastitis lactating goats experimentally infected with Staphylococcus aureus. Journal of Scientia Agricultura Sinica, 2003, 36(9): 1100-1104. (in Chinese) [11] 夏文江, 成章瑞. MCPKP: 一种微机用药物动力学专用程序. 中国 兽医科技, 1986, (4): 57-60. Xia W J, Cheng Z R. MCPKP-a tiny pharmacokinetics analysis program. Chinese Journal of Veterinary Science and Technology, 1986, (4): 57-60. (in Chinese) [12] 宋振玉, 刘耕陶. 当代药理学. 北京: 中国协和医科大学及北京医 科大学联合出版社, 1994: 107-122