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奥氟沙星静脉注射和肌肉注射后在鲫鱼(Carassius auratus)体内的药代动力学

Pharmacokinetics of orbifloxacin in crucian carp (Carassius auratus) after intravenous and intramuscular administration.

作者信息

Yang F, Yang F, Wang G, Shi W, Kong T, Yang P, Bai D, Zhou B

机构信息

College of Animal Science and Technology, Henan University of Science and Technology, Luoyang, China.

Jiangxi Bolai Pharmacy Co., Ltd., Jiujiang, China.

出版信息

J Vet Pharmacol Ther. 2018 Aug;41(4):599-604. doi: 10.1111/jvp.12495. Epub 2018 Feb 21.

Abstract

The pharmacokinetics of orbifloxacin was studied after a single dose (7.5 mg/kg) of intravenous or intramuscular administration to crucian carp (Carassius auratus) reared in freshwater at 25°C. Plasma samples were collected from six fish per sampling point. Orbifloxacin concentrations were determined by high-performance liquid chromatography with a 0.02 μg/ml limit of detection, then were subjected to noncompartmental analysis. After intravenous injection, initial concentration of 5.83 μg/ml, apparent elimination rate constant (λ ) of 0.039 hr , apparent elimination half-life (T ) of 17.90 hr, systemic total body clearance (Cl) of 75.47 ml hr  kg , volume of distribution (Vz) of 1,948.76 ml/kg, and volume of distribution at steady-state (Vss) of 1,863.97 ml/kg were determined, respectively. While after intramuscular administration, the λ , T , mean absorption time (MAT), absorption half-life (T ), and bioavailability were determined as 0.027 hr , 25.69, 10.26, 7.11 hr, and 96.46%, respectively, while the peak concentration was observed as 3.11 ± 0.06 μg/ml at 2.0 hr. It was shown that orbifloxacin was completely but relatively slowly absorbed, extensively distributed, and slowly eliminated in crucian carp, and an orbifloxacin dosage of 10 mg/kg administered intravenously or intramuscularly would be expected to successfully treat crucian carp infected by strains with MIC values ≤0.5 μg/ml.

摘要

在25°C淡水中饲养的鲫鱼(Carassius auratus)静脉注射或肌肉注射单剂量(7.5毫克/千克)奥比沙星后,对其药代动力学进行了研究。每个采样点从6条鱼中采集血浆样本。采用高效液相色谱法测定奥比沙星浓度,检测限为0.02微克/毫升,然后进行非房室分析。静脉注射后,分别测定初始浓度为5.83微克/毫升、表观消除速率常数(λ)为0.039小时⁻¹、表观消除半衰期(T½)为17.90小时、全身总体清除率(Cl)为75.47毫升·小时⁻¹·千克⁻¹、分布容积(Vz)为1948.76毫升/千克以及稳态分布容积(Vss)为1863.97毫升/千克。而肌肉注射后,λ、T½、平均吸收时间(MAT)、吸收半衰期(Tₐ)和生物利用度分别测定为0.027小时⁻¹、25.69小时、10.26小时、7.11小时和96.46%,同时在2.0小时观察到峰值浓度为3.11±0.06微克/毫升。结果表明,奥比沙星在鲫鱼体内吸收完全但相对缓慢,分布广泛且消除缓慢,静脉注射或肌肉注射10毫克/千克的奥比沙星剂量有望成功治疗感染MIC值≤0.5微克/毫升菌株的鲫鱼。

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