达氟沙星在健康和鳗弧菌感染牙鲆体内的药物代谢动力学比较

Comparative pharmacokinetics of danofloxacin in healthy and Vibrio anguillarum infected flounder Paralichthys olivaceus

  • 摘要: 牙鲆随机分为3组,单剂量静注(健康)和口灌(健康对照和鳗弧菌感染)达氟沙星,进行健康和鳗弧菌感染牙鲆比较药动学和生物利用度的研究。药物浓度用高效液相色谱法测定,数据采用MCP-KP自动化药动学分析程序进行分析。结果表明,健康牙鲆静脉注射达氟沙星(5 mg·kg-1)后,血药经时过程符合无吸收一室开放模型。口灌给药(10 mg·kg-1)健康及感染牙鲆的血药浓度与时间关系均符合一级吸收一室开放模型;肝脏和肾脏中药物浓度与时间关系均符合一级吸收二室开放模型。与健康牙鲆药动学参数相比较,达氟沙星在鳗弧菌感染牙鲆中的药时曲线下面积由256.07 mg·h-1·L-1降为209.18 mg·h-1·L-1,最大血药浓度由5.699 μg·mL-1降低为2.932 μg·mL-1,消除半衰期由27.758 h延长为46.195 h,生物利用度由71.21%降低为58.17%。

     

    Abstract: The founder Paralichthys olivaceus were divided into three groups randomly and the pharmacokinetics and bioavailability of danofloxacin were examined in healthy and Vibrio anguillarum infected founder Paralichthys olivaceus. Concentrations of dano floxacin were determined by the High Performance Liquid Chromatography and data were analyzed with the pharmacokinetic computer program MCP-KP. The results showed that blood concentration of danofloxacin in healthy P. olivaceus after intravascular administration (5 mg·kg-1 body weight) was described by a one-compartment open model with no absorption. The blood concentration-time curves after oral administration (10 mg·kg-1 body weight) in healthy and infected P. olivaceus all could be described by a one-compartment open model with the first order absorption; whereas the liver and kidney were both fit to the two-compartmental open model with the first order absorption. Compared with the healthy P. olivaceus the pharmacokinetic parameters of danofloxacin in infected founder had great changes, such as the area under concentration-time curve decreased from 256.07 mg·h-1·L-1 to 209.18 mg·h-1·L-1,the maximum drug concentration decreased from 5.699 μg·mL-1 to 2.932 μg·mL-1, the elimination half-life increased from 27.758 h to 46.195 h, and the bioavailability was 71.21% for healthy fish and 58.17% for infected fish.

     

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