硫酸阿米卡星在鳗鲡体内的药动学和残留研究

目的]研究硫酸阿米卡星在鳗鲡体内的药物代谢动力学及其在组织中的残留.方法]利用高氯酸提取、固相萃取净化组织,2,4,6-三硝基苯磺酸、吡啶、4-二甲基氨基吡啶、三氟乙酸柱前衍生后,采用高效液相紫外检测法测定硫酸阿米卡星在鳗鲡体内药代动力学和残留.结果]利用衍生法所得药物在0.05 ～50 μg/ml浓度范围内线性关系良好（R=0.9995）,最低检测限为0.05 μg/ml.血液和肌肉中的平均回收率分别为75.9％和76.9％.鳗鲡在（26±1）℃以50 mg/kg单剂量肌肉注射给药物后,鳗鲡血液中的药-时曲线符合一级吸收二室模型.达峰时间为0.597.h,分布半衰期为3.52 h,表明硫酸阿米卡星在鳗鲡体内吸收分布迅速.峰浓度为22.229μg/ml,消除半衰期为46.945 h,推测该药物可能残留时间较长.鳗鲡在（26±1）℃下50 mg/kg单剂量肌肉注射硫酸阿米卡星后,5d后在肌肉组织中未检出,19 d后血液中未检出.结论]鳗鲡肌肉注射阿米卡星后,停药期为475 ～ 513 d.

Studies on the Pharmacokinetics and Residue of Amikacin Sulfate in Anguilla japonica

Objective ] The aim of the research was to study the pharmacokinetics of amikacin sulfate in Anguilla japonica and its residue in tissues. Method] The-tissues were extracted with perchloric acid and purified by using solid-phase extraction. After pre-column derivatization with 2,4,6-trinitro-benzenesulfonic acid （ TNBS）, pyridine, 4-dimethylaminopyridine and triflouroacetic aid, the pharmacokinetics and residue of amikacin sulfate were determined by high performance liquid chromatography with ultraviolet detection method. Result] The obtained med- icine by derivative method showed a good linear relationship in the range of 0.05 - 50 ~g/ml （ R = 0. 999 5 ） and the lowest detection limit was 0.05 p~g/ml. The average recovery rate in blood and muscle was 75.9% and 76.9%. After 50 mg/kg amikacin sulfate was administrated by single-dose intramuscular injection at （26 ＋ 1 ） ~C, the drug concentration and time curve was accordant with a two-compartment open model. The peak time was 0. 597 h and distribution half-life was 3.52 h, which showed the absorption and distribution of amikacin sulfate in Anguilla japonica was rapid. The peak concentration was 22. 229 i.~g/ml and elimination half-time was 46. 945 h, it was deduced that the residual time of drug was longer. After 50 mg/kg amikacin sulfate was injected in muscle of AnguiUajaponica at（26 ~ 1 ） ~C ,amikacin sulfate wasn＇ t detec- ted in muscle tissues after 5 d,and amikacin sulfate wasn＇t detected in blood after 19 days. Conclusion] The withdrawal time of amikacin sulfate in muscle of Anguilla japonica was 475 -513 d after intramuscular injection.