达氟沙星在健康大菱鲆体内的药代动力学研究

Pharmacokinetics of danofloxacin in turbot Scophthalmus maximus following intravenous and oral administration

中文关键词: 达氟沙星  大菱鲆  药代动力学

英文关键词: Danofloxacin  Scophthalmus maximus  Pharmacokinetics

中文摘要:

      在水温16±0.6℃条件下，以20mg/kg鱼体重剂量对健康大菱鲆静脉注射和口服达氟沙星，利用高效液相色谱法测定96h内血浆和组织中的达氟沙星含量。DAS 2.0自动药动学软件分析表明，静注给药时，达氟沙星的血药经时过程符合零级吸收二室开放模型，表达方程式为C静注=45.74le-1.927t+7.332e-0.019t，消除半衰期(t1/2β)和药时曲线下面积(AUC0-t)分别为36.336h和431.981h·μg/ml；口服给药时，达氟沙星的血药经时过程符合一级吸收二室开放模型，表达方程式为 C口服=6.796e-0.05t+3.135e-0.005t-9.931e-0.11t，12h时血药浓度达到最大值(Cmax)5.312μg/ml，消除半衰期、药时曲线下面积和表观分布容积(Vd)分别为129.228h、284.915 h·μg/ml和2.986 L/kg；口服达氟沙星的生物利用度(F)为65.96%，肝脏和肾脏内的药物浓度较高，与血药浓度相似，而肌肉内较低。根据达氟沙星在大菱鲆体内的药代动力学特点及其对主要致病菌的体外抑菌参数指标，提出了口服给药方案：按12.17mg/kg体重/次，1日1次。

英文摘要:

      Danofloxacin, a third generation member of the quinolone family, it has been also used widely to prevent or treat bacterial diseases in fish farming in many countries. It has been studied in Paralichthys olivaceus, Acipenser schrenckii, and goldfish Carassius auratus Linnaeus, etc. However, to our knowledge, there are no studies concerning the pharmacokinetics of danofloxacin in turbot Scophthalmus maximus. In this study, the pharmacokinetics behavior of danofloxacin in turbot after intravenous and oral administration was investigated. Six fish were randomly selected from the tank (water temperature 16±0.6℃) and sampled at 15, 30min, and 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96h after intravenous and oral administration, respectively. The concentrations of danofloxacin were determined by HPLC. The data were analyzed with the pharmacokinetic program DAS 2.0. The results showed that the relationship of plasma concentration versus time for danofloxacin were best described as a two-compartment open model, and the pharmacokinetic equations were: Civ=45.741e-1.927t＋7.332e-0.019t, Cpo=6.796e-0.05t＋3.135e-0.005t－9.931e-0.11t. After the intravenous and oral administration, the main pharmacokinetic parameters were as follows: t1/2β 36.336h and 129.228h, AUC0-96h 431.981 and 284.915 h·μg/ml, respectively. After oral administration, the concentration of danofloxacin in liver and kidney was higher than in muscle, but was similar with the concentration in plasma. According to the danofloxacin pharmacokinetics and the minimal inhibitory concentration of most fish bacterial pathogens, the dosage regime of danofloxacin for treatment of fish bacterial diseases was calculated as a daily dosage of 12.17mg/kg by oral administration.