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甲砜霉素在鲤鱼中的药代动力学研究
潘明轩1,2,3, 李兆新1,3, 邢丽红1,3, 孙晓杰1,3, 彭吉星1,3, 董 晓1,2,3
1.中国水产科学研究院黄海水产研究所 青岛 266071;2.上海海洋大学食品学院 上海 201306;3.农业农村部水产品质量安全风险评估实验室 青岛 266071
摘要:
本实验在(26±2)℃的养殖水温下,采用高效液相色谱–串联质谱法(HPLC-MS/MS)研究了以30 mg/(kg·bw)的剂量对鲤鱼(Cyprinus carpio)进行单次投喂药饵后甲砜霉素(Thiamphenicol, TAP)在鲤鱼体内的药物代谢动力学。通过DAS 2.0动力学软件分析TAP在鲤鱼体内的药–时数据,结果表明符合一级吸收二室模型。TAP在肌肉、肾脏、肝脏、鱼皮、鳃、脾脏和血浆各组织的药物达峰时间(Tpeak)分别为16、2、16、8、0、2和16 h,达峰浓度(Cmax)分别为15.6、35.3、12.4、9.0、33.0、11.6 mg/kg和21.0 mg/L;药–时曲线下面积(AUC)分别为1084.5、1578.1、777.3、541.1、0.1、478.1 mg/(kg·h)和485.1 mg/(L·h),消除半衰期(t1/2β)分别为11.4、100.2、54.2、41.1、69.5、38.0和71.9 h。TAP在鲤鱼体内各组织的分布和消除速率相差较大;在肾脏中的药物达峰时间短且达峰浓度高于其他组织,其消除半衰期也明显高于其他组织,推测肾脏是鲤鱼体内TAP蓄积和代谢的主要器官。按照农业部《动物性食品中兽药最高残留限量》文件规定,TAP在水产动物中最高残留限量(MRL)不得高于50 μg/kg,本研究中,肌肉、肾脏、肝脏、鱼皮、脾脏和血浆的TAP残留量低于MRL的时间分别从第16、16、12、12、12、10和12天开始,将肌肉和肾脏作为TAP药物残留的靶组织,建议休药期不得低于16 d。
关键词:  甲砜霉素  代谢残留  鲤鱼  药代动力学
DOI:
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Drug Pharmacokinetic Study of Thiamphenicol in Cyprinus carpio
PAN Mingxuan1,2,3, LI Zhaoxin1,3, XING Lihong1,3, SUN Xiaojie1,3, PENG Jixing1,3, DONG Xiao1,2,3
1.Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao 266071;2.College of Food Science and Technology, Shanghai Ocean University, Shanghai 201306;3.Laboratory of Quality & Safety Risk Assessment for Aquatic Products,Ministry of Agriculture and Rural Affairs, Qingdao 266071
Abstract:
In this experiment, the water temperature was raised at (26±2)℃. The experiment used high performance liquid chromatography tandem mass spectrometry(HPLC-MS/MS) to study thiamphenicol in pharmacokinetics of carp with 30 mg/(kg·bw) single dose of carp feed. Data were analyzed using DAS 2 dynamics software, and the experimental results suggest a two-compartment model of primary absorption. The peak of thiamphenicol (TAP) in muscles, kidneys, liver, skin, gills, spleen, and plasma were 16, 2, 16, 8, 0, 2, 16 h; the Cmax were 15.6, 35.3, 12.4, 9.0, 33.0, 11.6 mg/kg, and 21.0 mg/L; the area under curve (AUC) was 1084.5, 1578.1, 777.3, 541.1, 0.1, 478.1 mg/(kg·h), and 485.1 mg/(L·h); the t1/2β was 11.4, 100.2, 54.2, 41.1, 69.5, 38.0, and 71.9 h. The results showed that the distribution and elimination rate of TAP in carp tissues varied greatly; the peak time of renal drugs is shorter; the peak concentration is higher than in other tissues, and the elimination half-life is higher than that in other tissues, which suggested that kidneys are the main organ of TAP accumulation and metabolism. In accordance with the Ministry of Agriculture, Animal Food in Veterinary Drugs Maximum Residue Limit document provides that the maximum of TAP in aquatic animal residue limit (MRL) shall not be higher than 50 μg/kg. In this experiment, the amounts of TAP residues in muscle, kidney, liver, skin, spleen, and plasma were lower than MRL, starting from 16, 16, 12, 12, 12, 10, and 12 d respectively. It is recommended that the period of withdrawal should be no less than 16 d.
Key words:  Thiamphenicol  Metabolic residue  Carp  Pharmacokinetics