甲砜霉素在大菱鲆体内的代谢及消除规律  

Pharmacokinetics and rules of residue elimination of thiamphenicol in Scophthalmus maximus

作　　者：吴少坤 林茂[1,2] 李忠琴 黄利强[1] 李江森[1] WU Shaokun;LIN Mao;LI Zhongqin;HUANG Liqiang;LI Jiangsen(Fisheries College,Jimei University,Xiamen 361021,China;Engineering Research Center of Fishery Drug,Xiamen 361021,China)

机构地区：[1]集美大学水产学院 [2]厦门市渔用药物工程技术研究中心,福建厦门361021

出　　处：《中国渔业质量与标准》2018年第2期42-48,共7页Chinese Fishery Quality and Standards

基　　金：海洋经济发展区域示范项目(16PZY002SF18);国家公益性行业(农业)科研专项(201203085);福建省自然科学基金(2014J01129)

摘　　要：为研究甲砜霉素(thiamphenicol)在大菱鲆(Scophthalmus maximus)体内的代谢动力学特征和残留消除规律,本研究采用液相色谱-串联质谱法检测甲砜霉素混饲口灌后在大菱鲆血浆、肌肉、肝脏和肾脏等样品中的时间-浓度变化。甲砜霉素以30 mg/kg的剂量单次混饲口灌,采集给药后48 h内的药时数据,并以DAS软件非房室模型进行分析,结果显示,甲砜毒素在大菱鲆血浆中达峰浓度(C_(max))和达峰时间(T_(max))分别为21.968μg/m L和9 h,药时曲线下面积[AUC_((0—∞))]为319.754 mg/(L·h),表观分布容积(Vz/F)为6.206 L/kg,平均滞留时间[MRT_((0—∞))]和消除半衰期(T1/2z)分别为33.984 h和45.841 h。甲砜霉素在大菱鲆的肌肉、肝脏和肾脏组织中达峰浓度(C_(max))分别至22.346、27.128和47.718μg/g;在肝脏中达峰时间较快(4 h),在肌肉和肾脏组织中均在9 h;在肾脏中的达峰浓度(C_(max)=47.718μg/g)和药时曲线下面积AUC(0-∞)最大,为517.768 mg/(L·h),表明肾脏对甲砜霉素的吸收能力最高;在肝脏中的平均滞留时间[MRT_((0—∞))=36.565 h]最长,消除半衰期T1/2z为42.370 h,即给药后48 h内甲砜霉素在肝脏中的消除较慢。甲砜霉素以60 mg/kg的高剂量单次给药后,采集30 d内的药时数据并以WT程序进行计算,结果显示甲砜霉素在大菱鲆血浆、肌肉、肝脏和肾脏中的理论休药期分别为8.90、10.64、18.19和23.95 d。本研究结果可为甲砜霉素在大菱鲆中的合理应用提供科学依据。In this paper,the pharmacokinetics and residue elimination rules of thiamphenicol in Scophthalmus maximus were studied.Liquid chromatography-tandem mass spectrometry(LC-MS)was used to detect the time-concentration data of thiamphenicol in the plasma,muscle,liver and kidney of Scophthalmus maximus after oral administration by gavage.Following the dose of 30 mg/kg body weight in 48 h,the pharmacokinetic parameters were computed by non-compartmental model using DAS software,whose results were area under the curve AUC(0-∞)of 319.754 mg/(L·h),apparent volume of distribution(Vz/F)of 6.206 L/kg,mean residence time MRT(0-∞)of 33.984 h,half-life(T 1/2z)of 45.841 h,maximum concentrations(C max)of 21.968μg/mL,and time to C max(T max)of 9 h.The maximum concentration(C max)in the muscle,liver and kidney tissues of Scophthalmus maximus was 22.346,27.128 and 47.178μg/g respectively.The time to T max of Liver(4 h)was faster than muscle(9 h)and kidney’s(9 h).The maximum concentration(C max=47.718μg/g)in the kidney and the under the curve[AUC(0-∞)=517.768 mg/(L·h)]were the largest,indicating that the kidney had the highest absorption capacity of the drug.The average retention time in the liver[MRT(0-∞)=36.565 h]is the longest,eliminating the half-life T 1/2z was 42.370 h,which cleared slowly the drug in the liver of 48 h after treatment.Following the dose of 60 mg/kg in 30 d,the rules of residue elimination were regressed by WT program.It was showed that the calculated withdrawal time of thiamphenicol in plasma,muscle,liver and kidney were 8.90,10.64,18.19 and 23.95 d,respectively.The presented study will provide scientific basis for thiamphenicol application to Scophthalmus maximus.[Chinese Fishery Quality and Standards,2018,8(2):42-48]

关 键 词：甲砜霉素 大菱鲆 药代动力学 残留 休药期 

分 类 号：S948[农业科学—水产养殖]