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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Key words:
- 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
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
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
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
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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