二氟沙星在大菱鲆(Scophthalmus maximus)体内的药代动力学特征

Pharmacokinetics of Difloxacin in Turbot (Scophthalmus maximus) Following Intravenous and Oral Administration

关键词:  二氟沙星  大菱鲆  药代动力学

Key words:  Difloxacin  Scophthalmus maximus  Pharmacokinetics

摘要:

为给大菱鲆临床安全用药提供依据，对二氟沙星在健康大菱鲆体内的药代动力学特征进行了研究。在水温为14–17℃条件下，以20 mg/kg体重剂量静脉注射和口服二氟沙星，分别于给药后的15、30 min和1、2、4、6、8、12、16、24、36、48、72、96 h采血及各组织，利用高效液相色谱测定各组织和血浆中的二氟沙星含量，采用DAS 2.0自动药动学软件分析药代动力学参数。结果显示，静注给药后，血浆中二氟沙星的药时曲线符合零级吸收二室开放模型，消除半衰期(t1/2β)和药时曲线下面积(AUC0-t)分别为30.02 h和440.37 h•μg/ml；口服给药后，血浆中二氟沙星的药时曲线符合一级吸收二室开放模型，4 h时血药浓度达到最大值(Cmax) 6.32 μg/ml，t1/2β和AUC0-t分别为94.72 h和246.66 h•μg/ml，生物利用度(F)为56.01%，肾脏和肌肉内的药物浓度较高，而肝脏内相对较低。拟合的最佳口服给药方案为：按鱼体重每次给药11.94 mg/kg，每日1次。

Abstract:

To investigate the pharmacokinetics of difloxacin in Scophthalmus maximus after intravenous and oral administration at 14−17℃ water temperature, several tissues and plasmas were collected at various time points to calculate the dosage regimen of difloxacin. Five fish were randomly selected from the tank and sampled at 15, 30 min and 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 h after intravenous and oral administration, respectively. The concentration of difloxacin was determined by the High Performance Liquid Chromatography. The data were analyzed with the pharmacokinetic program DAS 2.0. The results showed that the plasma concentration of difloxacin at each time point was best described as a two-compartment open model. The elimination half-life (t1/2β) was 30.02 h for intravenous administration, and the area under concentration-time curve (AUC0-t) was 440.37 h•μg/ml. The peak concentration (Cmax) by oral administration was 6.32 μg/ml at 4 h, and t1/2β was 94.72 h, and AUC0-t was 246.66 h•μg/ml. The concentration in muscle and kidney was higher than that in liver by oral administration. According to the difloxacin pharmacokinetics and the minimal inhibitory concentration of most fish bacterial pathogens, the recommended dosage of difloxacin was 11.94 mg/kg once per day by oral administration.