Shan Qi, Huang Heqing, Zheng Guangming, Yin Yi, Zhu Xinping, Ma Lisha, Zhou Hao, Xie Wenping, Li Lichun, Liu Shugui, Wang Jingxin
Key Laboratory of Recreational Fisheries Research, Ministry of Agriculture and Key Laboratory of Aquatic Animal Immune Technology of Guangdong Province, Pearl River Fisheries Research Institute, Chinese Academic of Fishery Science, Guangzhou, China.
Key Laboratory of Tropical and Subtropical Fishery Resource Application and Cultivation, Ministry of Agriculture, Pearl River Fisheries Research Institute, Chinese Academic of Fishery Science, Guangzhou, China.
Front Vet Sci. 2022 Apr 14;9:872828. doi: 10.3389/fvets.2022.872828. eCollection 2022.
The pharmacokinetics, tissue distribution, and elimination of enrofloxacin (ENR) and its metabolite ciprofloxacin (CIP) were investigated to the crucian carp () after single (20 mg/kg b. w.) and multiple oral administration (20 mg/kg b.w. one time daily for 5 days) at 28°C. The concentrations of ENR and CIP in the plasma and tested tissues (muscle/skin, liver, and kidney) were detected simultaneously by high-performance liquid chromatography (HPLC), and the pharmacokinetic data were analyzed with a non-compartmental model using WinNonLin 6.1 PK software (Pharsight Corporation, Mountain View, CA, USA). The pharmacokinetic characteristics of ENR in crucian carp exhibited slow absorption, wide tissue distribution, and long elimination half-life. In the single-dose group, the peak concentrations (Cmax) of ENR in the plasma, muscle/skin, liver, and kidney were 8.93 μg/mL, 13.9 μg/g, 31.2 μg/g, and 27.3 μg/g, respectively, observed at 3 h, 6 h, 1 h, and 3 h after dosing. The elimination half-lives (T ) of ENR in plasma, muscle/skin, liver, and kidney were calculated to be 67.4, 82.8, 94.4, and 114 h, respectively. In the multiple-dose group, the C of ENR in the plasma, muscle/skin, liver, and kidney were 18.4 μg/mL, 26.8 μg/g, 82.8 μg/g, and 74.5 μg/g, respectively, achieved at 3 h, 6 h, 1 h, and 1 h after the last dose. The T of ENR in the plasma, muscle/skin, liver, and kidney were calculated to be 76.4 h, 91.5 h, 114 h, and 148 h, respectively. During the multiple-dose administration, significant accumulations of ENR and CIP were observed in the plasma and tissues of crucian carp, possibly due to their long elimination half-lives. In both dose groups, the AUC for both ENR and CIP followed the order of liver > kidney > muscle/skin > plasma. The finding suggested that the liver may play an important role in the metabolism of ENR. According to the calculated PK/PD indices of C/minimum inhibitory concentrations (MIC) and AUC/MIC, the multiple-dose regimen would be highly effective against pathogenic bacteria with a MIC value of ≤ 1.84 μg/ml. Depletion studies indicated that a withdrawal period of at least 29 or 32 days was necessary to guarantee food security after single or multiple oral gavage administration at 28°C.
在28°C条件下，对鲫鱼单次（20 mg/kg体重）和多次口服给药（20 mg/kg体重，每日一次，共5天）恩诺沙星（ENR）及其代谢物环丙沙星（CIP）后的药代动力学、组织分布和消除情况进行了研究。采用高效液相色谱法（HPLC）同时检测血浆和受试组织（肌肉/皮肤、肝脏和肾脏）中ENR和CIP的浓度，并使用WinNonLin 6.1 PK软件（美国加利福尼亚州山景城Pharsight公司）的非房室模型分析药代动力学数据。鲫鱼中ENR的药代动力学特征表现为吸收缓慢、组织分布广泛和消除半衰期长。在单剂量组中，给药后3小时、6小时、1小时和3小时，血浆、肌肉/皮肤、肝脏和肾脏中ENR的峰浓度（Cmax）分别为8.93 μg/mL、13.9 μg/g、31.2 μg/g和27.3 μg/g。血浆、肌肉/皮肤、肝脏和肾脏中ENR的消除半衰期（T）分别计算为67.4、82.8、94.4和114小时。在多剂量组中，末次给药后3小时、6小时、1小时和1小时，血浆、肌肉/皮肤、肝脏和肾脏中ENR的C分别为18.4 μg/mL、26.8 μg/g、82.8 μg/g和74.5 μg/g。血浆、肌肉/皮肤、肝脏和肾脏中ENR的T分别计算为76.4小时、91.5小时、114小时和148小时。在多次给药期间，观察到鲫鱼血浆和组织中ENR和CIP有明显蓄积，可能是由于它们的消除半衰期长。在两个剂量组中，ENR和CIP的AUC均遵循肝脏>肾脏>肌肉/皮肤>血浆的顺序。这一发现表明肝脏可能在ENR的代谢中起重要作用。根据计算的C/最低抑菌浓度（MIC）和AUC/MIC的PK/PD指数，多剂量方案对MIC值≤1.84 μg/ml的病原菌将非常有效。耗竭研究表明，在28°C条件下单次或多次口服灌胃给药后，至少需要29或32天的停药期以确保食品安全。
