Pharmacokinetics and Residues of Mequindox in American Eel
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摘要: 在水温（25±1）℃条件下，分别采用口灌和浸浴的给药方式，以120 mg·kg-1的单剂量混饲口灌及5 mg·L-1浸浴18 h给予乙酰甲喹后，用高效液相色谱法测定血浆、肌肉、肝脏及肾脏中的药物浓度，研究不同给药方式下乙酰甲喹在美洲鳗鲡体内的药代动力学特征及残留情况。结果表明：乙酰甲喹原药在美洲鳗鲡体内吸收良好、代谢快、体内残留少。口灌给药后，血浆中药物浓度达峰时间Tmax为0.75 h，达峰质量浓度Cmax为4 115 μg·L-1，消除相半衰期T1/2为7.40 h，总体消除率CL/F为41.89 L·kg-1·h-1，72 h后血浆、肌肉、肝脏及肾脏中几乎检测不到原药；浸浴给药血浆中药物浓度于0.25 h达峰，达峰质量浓度Cmax为435.6 μg·L-1，消除相半衰期T1/2为0.26 h，总体消除率CL/F为1.241 L·kg-1·h-1，2.5 h后各组织中几乎检测不到原药。2种方式给药乙酰甲喹在美洲鳗鲡血浆中分布均符合药动学一室开放模型。Abstract: In the tank with a constant water temperature of 25±1℃, American eels were administered with mequindox (MEQ) for the study. The eels were either orally fed with a feed at a single MEQ dosage rate of 120 mg/kg, or placed in a water bath containing 5 mg MEQ/L for 18 h. Samples were collected periodically to obtain MEQ concentrations in the blood plasma, muscle, liver, and kidney of the eels by HPLC, while MEQ pharmacokinetics analyzed. The pharmacokinetic characteristics of MEQ were found to be fast absorbed, evenly distributed, rapidly eliminated, and left with low residues in the fish. Under the oral administration, the pharmacokinetics of the blood plasma showed a Tmax at 0.75 h, Cmax at 4 115 μg·L-1, T1/2 at 7.40 h, and CL/F at 41.89 L·kg-1·h-1. The concentrations of MEQ in the organs were below the detectable level after 72 h. For the medicated bath treatment, the pharmacokinetics of the eel blood plasma indicated Tmax to be 0.25 h, Cmax 435.6 μg·L-1, T1/2 0.26 h, and CL/F 1.241 L·kg-1·h-1. The MEQ in the organs became not detectable after 2.5 h. The distribution of plasma MEQ in the eels under either treatment fitted the one-compartment open model.
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Keywords:
- mequindox /
- american eel /
- pharmacokinetics /
- high performance liquid chromatography
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图 1 乙酰甲喹高效液相色谱
注：a.乙酰甲喹标准品，b.空白样品，c.给药样品，d.空白样品加标。
Figure 1. HPLC chromatograms and UV spectra of MEQ
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图 2 美洲鳗鲡口灌乙酰甲喹(120 mg·kg-1)后血浆中的药时曲线
Figure 2. Concentration-time curve on MEQ in eel plasma after oral administration of 120 mg·kg-1
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图 3 美洲鳗鲡口灌乙酰甲喹(120 mg·kg-1)后肌肉、肝脏和肾脏中的药物残留随时间变化情况
Figure 3. Concentration-time curves on MEQ in muscle, liver, and kidney of eels after oral administration of 120 mg·kg-1
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图 4 美洲鳗鲡浸浴乙酰甲喹(5 mg·L-1)后血浆中的药时曲线
Figure 4. Concentration-time curve on MEQ in eel plasma after bath treatment of 5 mg·L-1
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图 5 美洲鳗鲡浸浴乙酰甲喹(5 mg·L-1)后肌肉、肝脏和肾脏中的药物残留随时间变化情况
Figure 5. Concentration-time curve on MEQ in muscle, liver, and kidney of eels after bath treatment of 5 mg·L-1
表 1 美洲鳗鲡血浆、肝脏、肾脏和肌肉中乙酰甲喹的线性回归方程及相关系数
Table 1 Linear regression equations and coefficients for MEQ in plasma, liver, kidney, and muscle of American eels
样品 回归方程 相关系数/r 血浆 Y=151X-6360 0.9998 肝脏 Y=116X-1230 0.9993 肾脏 Y=123X-1462 0.9994 肌肉 Y=150X-25700 0.9990 
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表 2 回收率试验结果(n=6)
Table 2 Result of recovery rates (n=6)
组织 添加水平/
(μg·mL-1)平均回收率
/%RSD日内
/%RSD日间
/%肌肉 0.05 78.5 9.56 9.91 0.1 82.7 7.35 8.23 1.0 87.4 3.21 4.91 血浆 0.05 77.8 8.28 9.92 0.5 84.9 6.94 7.68 1.0 88.3 4.42 5.71 肝 0.05 76.4 9.12 9.04 0.1 87.1 5.93 6.38 1.0 89.5 4.25 4.67 肾 0.05 79.8 9.32 9.83 0.1 80.5 6.55 7.51 1.0 84.0 5.13 6.37
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表 3 口灌给药美洲鳗鲡对乙酰甲喹的药代动力学参数
Table 3 Pharmacokinetic parameters of mequindox in American eel afer oral administration
参数 单位 血浆 A μg·L-1 2864.5 α h-1 0.094 K h-1 2.786 Ka h-1 0.094 T1/2Ka h 7.398 CL/F L·kg-1·h-1 41.89 Vd/F L·kg-1 447.1 AUC μg·L-1·h-1 223.8 Tmax h 0.75 Cmax μg·L-1 4115
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表 4 浸浴给药美洲鳗鲡对乙酰甲喹的药代动力学参数
Table 4 Pharmacokinetic parameters of MEQ in eels after treatment in medicated bath
参数 单位 血浆 A μg·L-1 4028 α h-1 1.575 K h-1 15.41 Ka h-1 1.575 T1/2Ka h 0.44 CL/F L·kg-1·h-1 1.241 Vd/F L·kg-1 0.788 AUC μg·L-1·h-1 62 Tmax h 0.25 Cmax μg·L-1 435.6
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[1] 中国兽药典委员会.中华人民共和国兽药规范(一部)[S].北京:中国农业出版社, 1992. [2] 李秀颖.乙酰甲喹对青鱼细菌性肠炎病的治疗作用[J].吉林水利, 2009, 331(12):50. [3] 李锦泉, 赵武, 许力干, 等.猪痢疾的诊断与防制[J].畜牧与兽医, 2000, 134(14):62. http://www.cnki.com.cn/Article/CJFDTOTAL-XMYS200204017.htm [4] 刘迎春, 高怀涛.乙酰甲喹的合理应用[J].养禽与禽病防治, 2009, (3):42-43. http://www.cnki.com.cn/Article/CJFDTOTAL-YQYF200903023.htm [5] 陈灵.日本鳗鲡腐皮病的原发病原及其治疗试验[D].福州:福建农林大学, 2010. http://cdmd.cnki.com.cn/Article/CDMD-10389-2010181542.htm [6] 季勤龙.犊牛乙酸甲喹中毒[J].上海畜枚兽医通讯, 2005, (4):67. [7] 倪俊兵, 张加纯, 程素平.一例仔猪乙酞甲哇中毒的诊治[J].上海畜牧兽医通讯, 2007, (4):89. [8] 李世尧, 张俊文.鸡乙酰甲喹中毒的诊断和治疗[J].畜禽业, 2008, (2):75-76. http://www.cnki.com.cn/Article/CJFDTOTAL-XQYI200802038.htm [9] 张智辉, 姚绵鹏.种鸽痢菌净中毒的诊治[J].养禽与禽病防治, 2008(4):41. http://www.cnki.com.cn/Article/CJFDTOTAL-YQYF200804020.htm [10] LIU Y M, LJU Y C, DING H Z, et al.Pharmacokinetics of mequindox and its metabolites in swine[J].Agricullural Sciences in china, 2011, 10(12):1968-1976. DOI: 10.1016/S1671-2927(11)60198-3
[11] QI S N, LIU Y M, HE L M, et al. Metabolism of mequindox and its metabolites identification in chickens using LC-ITQ-orbitrap mass spectrometry[J].Journal of chromatography B, 2012, (881-882):96-106. http://d.scholar.cnki.net/detail/SJPD0006_U/SJPD120727140141
[12] 周艳飞, 李浛, 王亚芳. HPLC法测定乙酰甲喹和喹乙醇的方法研究[J].饲料研究, 2013, (4):67-69. http://www.cnki.com.cn/Article/CJFDTOTAL-SLYJ201304020.htm [13] 宫向红, 邹荣婕, 徐英江, 等.高效液相色谱法测定水产品中乙酰甲喹残留量[J].中国渔业质量与标准, 2012, 2(4):71-75. http://www.cnki.com.cn/Article/CJFDTOTAL-YYZL201204015.htm [14] 邹荣婕, 徐英江, 刘京熙, 等.乙酰甲喹在鲤鱼肌肉组织中的残留消除规律研究[J].中国农学通报, 2012, 28(29):137-141. http://www.cnki.com.cn/Article/CJFDTOTAL-ZNTB201229033.htm [15] HUANZHONG DING, YINGCHUN LIU, ZHENLING ZENG, et al. Pharmacokinetics of mequindox and one of its major metabolites in chickens after intravenous, intramuscular and oral administration[J]. Research in Veterinary Science, 2012, (93):374-377. https://www.ncbi.nlm.nih.gov/pubmed/21839487
[16] GUANGHUI L I, FAN YANG, LIMIN H E, et al. Pharmacokinetics of mequindox and its metabolites in rats after intravenous and oral administration[J].Research in Veterinary Science, 2012, (93):1380-1386. https://www.ncbi.nlm.nih.gov/pubmed/22459092
[17] 黄勇旗, 李引乾, 杨亚军, 等.乙酰甲喹在绵羊体内的药物动力学研究[J].西北农林科技大学学报:自然科学版, 2008, 36(2):177-181. http://www.cnki.com.cn/Article/CJFDTOTAL-XBNY200802016.htm
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