不同水温下盐酸氯苯胍在斑点叉尾血浆的药代动力学研究  

Pharmacokinetics of robenidine hydrochloride in plasma of channel catfish( Ictalurus punctatus) at different water temperatures

作　　者：余琳雪 刘永涛[2,3] 苏志俊 丁浩[1,2] 艾晓辉 YU Linxue;LIU Yongtao;SU Zhijun;DING Hao;AI Xiaohui(National Demonstration Center for Experimental Fisheries Science Education,Shanghai Ocean University,Shanghai 201306,China;Yangtze River Fisheries Research Institute,Chinese Academy of Fishery Sciences,Wuhan 430223,China;Key Labrotary of Control of Quality and Safety for Aquatic Products,Ministry of Agriculture and Rural Affairs,Wuhan 430223,China)

机构地区：[1]水产科学国家级实验教学示范中心(上海海洋大学),上海201306 [2]中国水产科学研究院长江水产研究所,湖北武汉430223 [3]农业农村部水产品质量安全控制重点实验室,湖北武汉430223

出　　处：《浙江农业学报》2018年第10期1640-1646,共7页Acta Agriculturae Zhejiangensis

基　　金：中国水产科学研究院基本科研业务费(2016HY-ZD1202;2018JBF02)

摘　　要：研究不同水温(18、28℃)条件下盐酸氯苯胍(robenidine hydrochloride,ROBH)在斑点叉尾(Ictalurus punctatus)血浆的药代动力学特征。以20 mg·kg^(-1)体质量剂量的盐酸氯苯胍单次口灌斑点叉尾,采用高效液相色谱-串联质谱法测定血浆中盐酸氯苯胍的浓度,内标法定量,并采用3p97药代动力学软件计算药代动力学参数、开展模型分析。结果表明,在不同水温条件下盐酸氯苯胍在斑点叉尾血浆的药时曲线均符合二室模型特征,动力学方程分别为C_(18℃)=4.17e^(-0.01t+)2.48e^(-0.008t)-6.65e^(-0.05t)和C_(28℃)=7.69e^(-0.02t+)0.13e^(-0.01t)-7.82e^(-0.27t)。血浆中盐酸氯苯胍达峰时间T_(peak)分别为42.36和10.03 h,峰浓度值C_(max)分别为3.51和5.76μg·m L^(-1),表观分布容积V/F(c)分别为3.79和2.78 L·kg^(-1),分布相的一级速率常数α分别为0.248和0.222h^(-1),消除相的一级速率常数β分别为0.006和0.007 h^(-1),吸收半衰期T_(1/2(ka))分别为14.67和2.54 h,消除半衰期T_(1/2(β))分别为85.52和58.63 h,中央室向周边室转运的一级速率常数K_(12)分别为0.000 2和0.000 2 h^(-1),周边室向中央室转运的一级速率常数K_(21)分别为0.009和0.01 h^(-1),药-时曲线下面积分别为554.18和326.74μg·m L^(-1)·h^(-1)。研究结果表明,盐酸氯苯胍在斑点叉尾体血浆的吸收、分布和消除受水温的影响显著,高水温条件下盐酸氯苯胍的达峰时间短,峰浓度值约是低水温时的2倍,水温对血药曲线下面积的影响较大,对肾清除率影响不大。研究结果为盐酸氯苯胍在斑点叉尾养殖过程中不同季节的合理使用提供一定理论依据。The pharmacokinetics of robenidine hydrochloride in the plasma of channel catfish(Ictalurus punctatus)at different water temperatures(18,28℃)were investigated in this study.The concentration of robenidine hydrochloride in the plasma of channel catfish was determined by HPLC-MS.Pharmacokinetic parameters were calculated by using the 3p97 Practical Pharmacokinetic Program software.The concentration-time data of robenidine hydrochloride in plasma were fitted to a two-compartment model at both 18℃and 28℃water temperature.The kinetic equations were C 18℃=4.17e-0.01 t+2.48e-0.008 t-6.65e-0.05 t,C 28℃=7.69e-0.02 t+0.13e-0.01 t-7.82e-0.27 t,respectively.The major pharmacokinetic parameters at water temperature 18℃and 28℃were as follows:The time point of maximum plasma concentration(T peak)was 42.36 and 10.03 h,respectively,peak plasma concentration(C max)was 3.51 and 5.76μg·mL-1,respectively.Relatively apparent distributed volume V/F(c)was approached to 3.79 and 2.78 L·kg-1,respectively.The distribution rate constantαwas 0.248 and 0.222 h-1,respectively.The elimination rate constantβwas 0.006 and 0.007 h-1,respectively.The absorption half-time[T 1/2(ka)]was 14.67 and 2.54 h,respectively.The elimination half-time[T 1/2(β)]was 85.52 and 58.63 h,respectively.First-order rate constant for drug distributions from central compartment to peripheral compartment(K 12)was 0.000 2 and 0.000 2 h-1,respectively.First-order rate constant for drug distributions from peripheral compartment to central compartment(K 21)was 0.009 and 0.01 h-1,respectively.The areas under the curve was 554.18 and 326.74μg·mL-1·h-1,respectively.The results showed that the temperature could significantly affect the absorption,distribution and elimination of robenidine hydrochloride in the plasma of channel catfish.Under high water temperature,the peak time of robenidine hydrochloride was short,the peak concentration value was about twice of that at low water temperature,and the water temperature had a greater influence on the areas unde

关 键 词：盐酸氯苯胍 斑点叉尾 药代动力学 水温 

分 类 号：S948[农业科学—水产养殖]