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两种水温下单剂量口服给药时氟苯尼考在团头鲂(Megalobrama amblycephala)体内的药代动力学

Pharmacokinetics of florfenicol in blunt-snout bream (Megalobrama amblycephala) at two water temperatures with single-dose oral administration.

作者信息

Huang Yuqing, Chen Xiaoxuan, Wang Huan, Zhao Hui, Luo Yaner, Wu Zhixin

机构信息

College of Fisheries, Huazhong Agricultural University/Key Lab of Freshwater Animal Breeding, Ministry of Agriculture/Hubei Engineering Technology Research Center for Aquatic Animal Diseases Control and Prevention/Freshwater Aquaculture Collaborative Innovation Center of Hubei Province, Wuhan, China.

出版信息

J Vet Pharmacol Ther. 2019 Sep;42(5):564-571. doi: 10.1111/jvp.12773. Epub 2019 Jun 14.

Abstract

The pharmacokinetics and residue elimination of florfenicol (FFC) and its metabolite florfenicol amine (FFA) were studied in healthy blunt-snout bream (Megalobrama amblycephala, 50 ± 10 g). The study was conducted with a single-dose (25 mg/kg) oral administration at a water temperature of 18 or 28°C, while in the residue elimination study, fish were administered at 25 mg/kg daily for three consecutive days by oral gavage to determine the withdrawal period (WDT) at 28°C. The FFC and FFA levels in plasma and tissues (liver, kidneys and muscle) were analysed using high-performance liquid chromatography (HPLC). A no-compartment model was used to analyse the concentration versus time data of M. amblycephala. In the two groups at 18 and 28°C, the maximum plasma concentration (C ) of FFC was 5.89 and 6.21 μg/ml, while the time to reach C (T ) was 5.97 and 2.84 hr, respectively. These suggested that higher temperature absorbed more drug and more quickly at M. amblycephala. And the elimination half-life (T ) of FFC was calculated as 26.75 and 16.14 hr, while the total body clearance (CL) was 0.09 and 0.15 L kg  hr , and the areas under the concentration-time curves (AUCs) were 265.87 and 163.31 μg hr/ml, respectively. The difference demonstrated that the elimination rate of FFC in M. amblycephala at 28°C was more quickly than that at 18°C. The results of FFA showed the same trend in tissues of M. amblycephala. After multiple oral doses (25 mg/kg daily for 3 days), the k (eliminate rate constant) of FFA in M. amblycephala muscle was 0.017, the C (initial concentration) was 3.07 mg/kg, and the WDT was 10 days (water temperature 28°C).

摘要

研究了氟苯尼考(FFC)及其代谢物氟苯尼考胺(FFA)在健康团头鲂(Megalobrama amblycephala,50±10克)体内的药代动力学和残留消除情况。在水温为18或28°C时,以单剂量(25毫克/千克)口服给药进行研究,而在残留消除研究中,通过口服灌胃以25毫克/千克的剂量连续三天给鱼给药,以确定28°C时的休药期(WDT)。使用高效液相色谱法(HPLC)分析血浆和组织(肝脏、肾脏和肌肉)中的FFC和FFA水平。采用非房室模型分析团头鲂的浓度-时间数据。在18°C和28°C的两组中,FFC的最大血浆浓度(Cmax)分别为5.89和6.21微克/毫升,而达到Cmax的时间(Tmax)分别为5.97和2.84小时。这表明在团头鲂中,较高温度下药物吸收更多且更快。FFC的消除半衰期(T1/2)计算为26.75和16.14小时,总体清除率(CL)为0.09和0.15升·千克-1·小时-1,浓度-时间曲线下面积(AUCs)分别为265.87和163.31微克·小时/毫升。差异表明,28°C时团头鲂体内FFC的消除速率比18°C时更快。FFA在团头鲂组织中的结果显示出相同趋势。多次口服给药(每天25毫克/千克,共3天)后,团头鲂肌肉中FFA的k(消除速率常数)为0.017,C0(初始浓度)为3.07毫克/千克,休药期为10天(水温28°C)。

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