恩诺沙星及其代谢物环丙沙星在大黄鱼体内的代谢动力学

Pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin in Larimichthys crocea

在(20±3)℃水温条件下,对大黄鱼肌注50 mg/kg恩诺沙星后,在不同的时间点取样,用高效液相色谱-串联质谱法测定血浆、肌肉、肝脏和性腺中的恩诺沙星及其代谢产物环丙沙星含量水平,研究恩诺沙星在大黄鱼体内的代谢及消除规律。结果表明,肌注给药后,恩诺沙星在大黄鱼体内的药时数据符合二室开放模型,其在血浆、肌肉、肝脏和性腺中的达峰时间(T_(max))分别为0.170、0.500、1.000、1.000 h,分布半衰期(T_(1/2α))分别为1.085、12.579、7.155、18.642 h,消除半衰期(T_(1/2β))分别为30.484、51.971、47.823、69.315 h;恩诺沙星主要代谢产物环丙沙星在大黄鱼体内的药时数据不符合一室和二室模型。实验结果表明,恩诺沙星在大黄鱼体内吸收分布迅速,消除较快。以肌肉作为靶组织,根据休药期公式,计算得到恩诺沙星在大黄鱼体内的休药期为18.7 d。因此,在本实验条件下,建议休药期不低于19 d。本研究结果可为大黄鱼养殖过程中科学使用恩诺沙星提供参考。

In this study the pharmacokinetics and residues elimination of enrofloxacin in Larimichthys crocea were investigated at water temperature of( 20 ± 3) ℃. After intramuscular injection of enrofloxacin in dose of 50 mg/kg,the concentration of enrofloxacin and its metabolite—ciprofloxacin in the plasma,muscle,liver and gonad of Larimichthys crocea were determined by high performance liquid chromatography tandem mass spectrometry. The results showed that the concentration-time course of enrofloxacin in Larimichthys crocea conformed to the two-compartment open model. The time to peak( T_(max)) of plasma,muscle,liver and gonad were 0. 170,0. 500,1. 000 and 1. 000 h,respectively,and the distribution half-life( T_(1/2α)) were 1. 085,12. 579,7. 155 and 18. 642 h,respectively,and the elimination half-life( T_(1/2β)) were 30. 484,51. 971,47. 823 and 69. 315 h. The concentration-time course of ciprofloxacin conformed to either the one-compartment or two-compartment open model. The absorption,distribution and elimination of enrofloxacin in Larimichthys crocea were relative fast. The muscle was found as target tissue and the withdrawal time was calculated as 18. 7 days by the typical formula of withdrawal time. Therefore,the withdrawal time of enrofloxacin in Larimichthys crocea was suggested more than 19 days. The data is of great benefit for practical applications of enrofloxacin in Larimichthys crocea.