Studies on pharmacokinetics of avermectin in grass carp (Ctenopharyngodon idellus) | 阿维菌素在草鱼体内的药物代谢动力学研究

中国人. 研究阿维菌素在草鱼体内的药物代谢动力学，为实际生产中阿维菌素的使用提供理论指导。用初始质量浓度为0.3μg/L的阿维菌素水溶液药浴草鱼，于给药后0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 144, 216, 336, 528和576 h采取血浆、肌肉+皮、肝脏、肾脏、鳃等样品，采用高效液相色谱-荧光法测定阿维菌素在草鱼血浆中的质量浓度及在组织中的含量，数据经3P97药动学软件分析。在(26.0±1.0) ℃的水温条件下，阿维菌素单剂量浸泡给药0.3 μg/L，血药经时过程符合二室开放式模型。主要药动学参数如下：分布半衰期(T1/2α) 34.2 h，吸收半衰期(T1/2(ka))15.61 h，消除半衰期(T1/2β)163.22 h，药时曲线下面积(AUC)2 486.02 (μg•h)/L，达峰时间(Tpeak)40.75 h，峰质量浓度(Cmax)11.92 μg/L。药后72 h时草鱼肌肉、肝脏、肾脏和鳃中阿维菌素含量均达到最高值，其中肝脏中的含量最高，达到17.8 μg/kg，其后依次为肾脏(12.1μg/kg)、肌肉(10.7 μg/kg)和鳃组织(5.2μg/kg)，血浆中阿维菌素含量在48 h达到最高(11.2μg/L)。肝脏、肾脏和鳃组织中阿维菌素含量均呈“双峰”曲线，前两者在144 h时都有第2次吸收高峰，分别为15.0和8.4 μg/kg。草鱼血浆及各组织中阿维菌素在给药后24 d未检出，考虑到临床应用情况的复杂性及理论值与实测值之间的差距，建议对草鱼单剂量(0.3μg/L)药浴阿维菌素后的休药期为24 d。

英语. The study was conducted to investigate the pharmacokinetic of avermectin in grass carp which would provide guide to correctly use avermectin. Bathing administration grass carp with initial concentration of 0.3 μg/L avermectin solution, after administration 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 144, 216, 336, 528 and 576 hours to take the plasma, muscle+skin, liver, kidney and gill samples, the concentration of avermectin in grass carp plasma and the content of tissues were determined by using the high performance liquid chromatography with fluorescence detector. Pharmacokinetic parameters were analyzed with the pharmacokinetic computer program 3P97. The grass carps were taken single-dose avermectin 0.3 μg/L by bathing administration when the water temperature was at (26.0±1.0) ℃, the plasma concentration time data of avermectin could be described by a two-compartment open model. The main pharmacokinetic parameters were as follows: The distribution half-life (T1/2α) was 34.2 h, the absorption half-life (T1/2(ka)) 15.61 h, the elimination half-life (T1/2β) 163.22 h, the area under the serum concentration-time curve (AUC) .2 486.02 (μg•h)/L, the time-point of maximum plasma concentration of the drug (Tpeak) and the maximum plasma concentration (Cmax) calculated 40.75 h and 11.92 μg/L. The content of avermectin reached the highest value in grass carp muscle, liver, kidney and gill tissues 72 h after administration, and which was the highest valued 17.8 μg/kg in the liver, followed by kidney(12.1 μg/kg), muscle (10.7 μg/kg) and gill (5.2 μg/kg), however the highest content of avermectin valued 11.2 μg/L appeared at 48 h after administration. The content of avermectin in the liver, kidney and gill tissues showed a “Twin Peaks” curve, the former two in the 144 h had a second absorption peak, respectively 15.0 μg/kg and 8.4 μg/kg. The avermectin in grass carp plasma and others tissues were not detected after the administration of 24 d. Considering the complicacy of avermectin in clincial applications, and difference between formula calculation and the fact, it was suggested WDT was 24 d after following single bathing administration at a dose of 0.3 μg/L.