喹乙醇在鲤体内的药物代谢动力学及组织浓度
STUDIES ON PHARMACOKINETICS AND TISSUE CONCENTRATION OF OLAQUINDOX IN COMMON CARPS
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摘要: 采用高效液相色谱法测定了鲤血浆及组织中喹乙醇的浓度.该法采用C18色谱柱,流动相为甲醇-三蒸水(1:8),检测波长为372nm,样品用1%的三氯乙酸沉淀蛋白,离心取上清液进样.该法灵敏、简便、准确、喹乙醇在0.2-2.6μg/mL浓度范围内线性关系良好,检测限为0.04μg/g,平均回收率为8.93%-100.2%,不同浓度水平的日内和日间精密度测定结果均小于10%.以30mg/kg鱼体重的剂量口灌给药,通过对喹乙醇在鲤体内的血药浓度经时曲线过程分析,发现其符合一级吸收一室开放模型,主要动力学参数如下:消除相半衰期T1/2k.876h,吸收相半衰期T1/2ka1.466h,达峰时间Tp3.913h,达峰浓度Cmax30.2ug/mL,血药浓度-时间曲线下面积AUC 406.92mg/L·h;并对用药后组织药物浓度和单次、多次灌药后肌肉中喹乙醇的残留量及以原型排出体外的喹乙醇进行了测定,获得了单次灌药后鲤肌肉、肝脏、肾脏和多次灌药后鲤肌肉中喹乙醇的代谢规律,测得原型药物排出体外的量占总灌药量的6.9%.该项研究全面了解了喹乙醇在鱼体内的药动学特征,对确定合理的临床用药方案以及无公害水产品中药物残留监测提供了可靠的理论依据.Abstract: The concentration of olaquindox in the plasma and tissues of common carps was determined by high performance liquid chromatography(HPLC). Using a C18 column, the mobile phase consisted of methanol/tridistilled water (15:85). The UV detection wavelength was 372 nm. Samples were deproteined with trichloro acetic acid. The precipitated mixture was shaken and then centrifuged, the filtrate was evaporated to dryness. Within the range of 0.2-25.6 μg/mL, Olaquindox had a good linearity. The detectability was 0.04 μg/g and the average recovery of olaquindox was 85.93%-100.2%. The within day and day to day precision expressed by RSD was less than 10% at three drug levels. Pharmacokinetics parameters and residues of olaquindox were investigated in common Carps, after orally administered at a dose of 30mg/kg fish, The C T curve was in accordance with one-compartment open model with the first order absorption. The pharmacokinetic parameters of olaquindox in carps are as follows: the elimination half life(T1/2k) is 5.876h, the distribution half life(T1/2ka) is 1.466h, the peak time (Tp) is 3.913h, the peak concentration (Cmax) is 30.25ug/mL and the area under the curve(AUC) is 406.92 mg/L·h. By means of the determination of contents of olaquindox in tissus, its remnant in carp musles after oral administration with a single dose and several doses and the olaquindox excreted in the prototype. The rhythms were found in the metabolism of olaquindox in muscles, liver and kindey after oral delivery in single dose and in muscles after oral delivery in several doses. The drug excreted in the prototype accounted for 6.9% of the total amount of the drug administered. The optimum drug feeding programe and drug administration ceasing period were suggested.
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Keywords:
- Olaquindox /
- Tissue concentration /
- Conmon carp
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