氟甲喹在大菱鲆体内的药代动力学研究

摘要

为探讨氟甲喹在大菱鲆体内的药代动力学特征,在水温14~17℃条件下,以20 mg/kg的剂量静脉注射和口服氟甲喹,分别于给药后15、30 min和1、2、4、6、8、12、16、24、36、48、72、96 h采血及各组织,利用高效液相色谱法测定血浆和各组织中的氟甲喹含量,采用DAS 2.0药动学软件中统计矩方法分析药代动力学参数。结果显示,静注给药后,血浆中氟甲喹的表观分布容积为5.46 L/kg,消除半衰期为56.93 h,曲线下面积、生物利用度分别为220.32 h·mg/L、100%；口服给药后,血浆中氟甲喹的曲线下面积、生物利用度分别为95.85 h·mg/L和43.51%,达峰时间为16 h,表观分布容积为4.21 L/kg,消除半衰期为14.12 h。结果表明,静注和口服氟甲喹在大菱鲆体内组织分布均较广,但静注消除慢,口服吸收差、消除快。口服给药后,血浆中氟甲喹浓度在24 h内高于对常见病菌的抑菌浓度,因此,每天以20 mg/kg的剂量给药1次,可对常见细菌疾病起到较好防治效果。%The purpose of this study was to investigate the pharmacokinetics behavior of flumequine,and calculate the dosage regimen of flumequine in Scophthalmus maximus. Six fish were randomly selected from the tank and sampled at 15,30 min and 1,2,4,6,8,12,16,24,36,48,72,96 h after intravenous and oral administration at 20 mg/kg flumequine,respectively,at 14—17 ℃ water temperature. The con-centrations of flumequine were determined by the high performance liquid chromatography. The data were analyzed with the pharmacokinetic program DAS 2 . 0 . The results showed that the apparent distribution volume,the elimination half-life, the area under concentration-time curve and the bioavailability were 5. 46 L/kg,56. 93 h,220. 32 h·mg/L and 100%,respectively,after intravenous administration. After oral administration, the area under concentration-time curve was 95. 85 h·mg/L,the bioavailability was 43. 51%,the time to peak concentration was 16 h,the apparent distribution volume was 4. 21 L/kg,and the elimination half-life was 14. 12 h. The results indicated that an adequate distribution from turbot plas-ma to various tissues after intravenous and oral administration,however,elimination rate was faster by oral administration than by intramuscular administration. According to the flumequine pharmacokinetics and the minimal inhibitory concentration of most fish bacterial pathogens,this study indicates that it is possible to obtain therapeutic flumequine blood concentrations via oral administration in turbot with the dose of 20 mg/kg at the interval of one day.