恩诺沙星及其代谢物环丙沙星在方斑东风螺体内药代动力学及残留消除规律研究  

Pharmacokinetics and residual elimination pattern of enrofloxacin and its metabolite ciprofloxacin in Babylonia areolate

作　　者：邓东 文永森 刘晓坤 吕文刚[1,2,3] 陈景雷 陈景步 DENG Dong;WEN Yongsen;LIU Xiaokun;LYU Wengang;CHEN Jinglei;CHEN Jingbu(Fisheries College,Guangdong Ocean University,Zhanjiang 524088,China;Invertebrate Science and Technology Innovation Center,Zhanjiang 524088,China;Hainan Kangguan Biotechnology Co.,Ltd.,Wenchang 571300,China)

机构地区：[1]广东海洋大学水产学院,广东湛江524088 [2]广东省无脊椎动物科技创新中心,广东湛江524088 [3]海南康冠生物科技有限公司,海南文昌571300

出　　处：《南方水产科学》2024年第6期176-186,共11页South China Fisheries Science

基　　金：广东省现代化海洋牧场适养品种核心技术攻关项目(2024-MRB-00-001);国家重点研发计划“蓝色粮仓”科技创新专项(2018YFD0901401);国家自然科学基金青年科学基金项目(31702325)。

摘　　要：近年来,养殖方斑东风螺(Babylonia areolata)体内的恩诺沙星残留问题频发,为揭示恩诺沙星及其代谢物在方斑东风螺体内的药代动力学规律,并制定出合理的给药方法与休药期。以方斑东风螺为研究对象,在(24.5±2.5)℃的养殖水温下,对方斑东风螺伴饵投喂20 mg·kg^(-1)的恩诺沙星混合液,分别于给药后的第0.17、第0.25、第0.5、第1、第2、第4、第12、第24、第48、第72、第120、第168、第240、第360小时分期采集组织,采用岛津8050LCMS/MS仪器检测各时期组织中的药物浓度。结果显示,药时数据适用于非房室模型,恩诺沙星在腹足肌肉、吻管(含食道腺)、肝脏中的达峰浓度(Cmax)分别为7.82、10.5、31.47 mg·kg^(-1),环丙沙星(代谢物)的Cmax分别为0.72、0.89、1.21 mg·kg^(-1);恩诺沙星的达峰时间(tmax)分别为1、4、4 h,环丙沙星的tmax分别为4、12、4 h;恩诺沙星的消除半衰期(t1/2z)分别为38.22、52.44、62.40 h,环丙沙星的t1/2z分别为66.23、33.11、27.06 h;各组织理论休药期分别为16.94、16.79、17.99 d。结果表明,各组织中Cmax/MIC>10,故20 mg·kg^(-1)的恩诺沙星混合液适用于治疗由哈维氏弧菌(Vibrio harveyi,MIC,0.45 mg·L^(-1))引发的东风螺疾病。研究建议休药期不低于440.76度日(℃·d),给药方案为每2天1次,共3次。In recent years,frequent occurrence of enrofloxacin residues in breeding snail(Babylonia areolate)has been a problem.To reveal the pharmacokinetic characteristics of enrofloxacin and its metabolites in B.areolate,and to design a rational dosing method and the rest period,we fed B.areolate with 20 mg·kg^(-1) of enrofloxacin mixture at water temperature of(24.5±2.5)℃,and then sampled at 0.17th,0.25th,0.5th,1st,2nd,4th,12th,24th,48th,72nd,120th,168th,240th and 360th hour after the dosing.Shimadzu 8050 LC-MS/MS was used to determine the drug concentration in the tissues in each period.The results show that the drug-time data applied to the non-atrial models in Gastropod muscle,proboscis(Including esophageal glands)and liver:the Cmax of enrofloxacin was 7.82,10.5 and 31.47 mg·kg^(-1),respectively;the Cmax of ciprofloxacin(Metabolite)was 0.72,0.89 and 1.21 mg·kg^(-1),respectively;the enrofloxacin tmax was 1,4 and 4 h,respectively;the ciprofloxacin tmax was 4,12 and 4 h,respec-tively;the enrofloxacin t1/2z was 38.22,52.44 and 62.40 h,respectively;the ciprofloxacin t1/2z was 66.23,33.11 and 27.06 h,respectively;the theoretical drug rest period was 16.94,16.79 and 17.99 d,respectively.The results indicate that for all tissues,20 mg·kg^(-1) of enrofloxacin mixture with the Cmax/MIC over 10 is suitable for the treatment of B.areolate disease caused by Vibrio harveyi(MIC,0.45 mg·L^(-1)).It is recommended that the drug rest period should not be less than 440.76℃·d and the dosing should be once every 2 d,a total of 3 times.

关 键 词：方斑东风螺 恩诺沙星 药代动力学 药物残留 休药期 

分 类 号：S948[农业科学—水产养殖]