2021, 36(6): 985-994. doi: 10.16535/j.cnki.dlhyxb.2021-017
关键词： 虹鳟 , 恩诺沙星 , 环丙沙星 , 剂量 , 代谢 , 残留 , 休药期
Keywords： Oncorhynchus mykiss , enrofloxacin , ciprofloxacin , dose , metabolism , residue , withdrawal time
为研究不同给药剂量下恩诺沙星（enrofloxacin，ENR）及其代谢物环丙沙星（ciprofloxacin，CIP）在虹鳟Oncorhynchus mykiss（体质量70.48 g±5.41 g）体内的代谢和消除规律，挑选健康虹鳟257尾，分为低剂量组（126尾，随机分为21个亚组，每组6尾）和高剂量组（132尾，随机分为22个亚组，每组6尾），在（15±2）℃条件下，分别以20、50 mg/kg生产实际使用剂量ENR对虹鳟进行单次口灌，于不同时间点采集其肝脏、肌肉、皮肤、肾脏、血浆和剩余组织，经高效液相色谱-串联质谱测定各组织药物浓度，采用DAS 2.0药代动力学软件用非房室模型统计矩方法分析药代参数并进行比较。结果表明：20 mg/kg剂量下，ENR在虹鳟肝脏、肌肉、皮肤、肾脏、剩余组织和血浆的药物达峰浓度（Cmax）值分别为13.349、11.164、23.378、114.196、33.762 mg/kg和3.361 mg/L，药物消除半衰期（t1/2z）分别为100.928、60.780、67.283、111.586、56.523、320.705 h；50 mg/kg剂量下，ENR在虹鳟对应组织的Cmax值分别为43.302、35.909、53.315、305.098、121.254 mg/kg和8.456 mg/L，t1/2z分别为204.193、115.639、102.405、121.852、201.834、325.593 h；两种剂量下虹鳟各组织均能检出环丙沙星，且高剂量下ENR及其代谢物CIP在虹鳟体内的吸收速度及程度均大于低剂量组，两种剂量下ENR和CIP均分别在虹鳟肾脏和肝脏中富集含量最高，高剂量下ENR消除速度较快，但残留时间较长。研究表明，在（15±2）℃下，建议ENR 20 mg/kg剂量对虹鳟单次口服给药休药期不低于768 h（32 d），50 mg/kg剂量下休药期不低于1 008 h（42 d）。
The concentrations of enrofloxacin (ENR) and its metabolite ciprofloxacin (CIP) in liver, muscle, skin, kidney, plasma, and carcass tissues were determined in rainbow trout Oncorhynchus mykiss with body mass of (70.48±5.41)g orally administrated by ENR at a dose of 20 mg/kg (low dose group)and 50 mg/kg (high dose group) at (15±2)℃ by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), and then the pharmacokinetic parameters were described by a non-compartmental analysis using DAS 2.0 software to probe into the pharmacokinetics and residue elimination of ENR and its metabolite CIP in rainbow trout. The results showed that the Cmax values of ENR were found to be 13.349 mg/kg in liver, 11.164 mg/kg in muscle, 23.378 mg/kg in skin, 114.196 mg/kg in kidney, 33.762 mg/kg in carcass, and 3.361 mg/L in plasma of the rainbow trout in low dose group, and the t1/2z values to be 100.928 h in liver, 60.780 h in muscle, 67.283 h in skin, 111.586 h in kidney, 56.523 h in carcass and 320.705 h in plasma of the rainbow trout in low dose group. At the dose of 50 mg/kg, the Cmax value of ENR was 43.302 mg/kg in liver, 35.909 mg/kg in muscle, 53.315 mg/kg in skin, 305.098 mg/kg in kidney, 121.254 mg/kg in carcass, and 8.456 mg/L in plasma of the rainbow trout, and the t1/2z values were 204.193 h in liver, 115.639 h in muscle, 102.405 h in skin, 121.852 h in kidney, 201.834 h in carcass, and 325.593 h in plasma of the rainbow trout. CIP was detected in all tissues of the rainbow trout in high and low dose groups, with more rapid absorption of ENR and CIP in rainbow trout in high dose groups than those in low dose group. The maximal concentrations of ENR and CIP were observed in the kidney and liver of rainbow trout. ENR elimination was found to be faster in high dose group, with the long residual time. In conclusion, it is recommended that the withdrawal period of a single dose of 20 mg/kg ENR after oral administration in rainbow trout be not less than 768 h (32 d), and the withdrawal period at a dose of 50 mg/kg be not less than 1 008 h (42 d).
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