【摘要】 采用以氯唑沙宗为底物探针的药代动力学方法研究氟苯尼考对鲫鱼细胞色素P450 2E1活性的影响。试验组鲫鱼每日经口给予氟苯尼考100 mg/kg(按体重给药,下同),连续5 d后,与对照组鲫鱼同时一次性腹腔注射氯唑沙宗10 mg/kg,用高效液相色谱法测定氯唑沙宗在鲫鱼体内不同时间点的血药浓度,并计算药代动力学参数。结果表明,氯唑沙宗在两组鲫鱼体内代谢的药时数据均符合二室模型;与对照组相比,试验组氯唑沙宗的半衰期增加了5倍(P<0.01),药时曲线下面积增加了3.3倍(P<0.01),总清除率减少了83.8%(P<0.01)。提示,氟苯尼考对鲫鱼CYP2E1具有显著的抑制作用。其他药物与氟苯尼考合用时,其有效性和安全性可能会受到影响。更多还原

【Abstract】 The effect of florfenicol(FFC) on the activity of cytochrome P450 2E1 in Carassius auratus was evaluated by pharmacokinetics using chlorzoxazone(CZX) as a specific substrate.FFC was administered orally for 5 days at 100mg/kg every day for the experimental group.Control fish were given an equal volume of normal saline only.On day 6,fish were given an intraperitoneal injection with 10mg/kg CZX.The plasma concentration of CZX was determined by high performance liquid chromatography(HPLC).The pharmacokinetic parameters were calculated.The results showed that the concentration-time data of CZX in the two groups were fitted to the two-compartment model.Compared with the normal saline-treated control group,elimination half life was increased by 5 fold(P<0.01),an area under the curve was increased by 3.3 fold(P<0.01),and total clearance was shortened by 83.8%(P<0.01) in the FFCtreated group.The results indicate that the activity of CYP2E1 is markedly inhibited by florfenicol.A drug’s efficacy and safety may be affected when concomitantly used with florfenicol.更多还原