氯唑沙宗评价氟苯尼考对鲫鱼CYP2E1活性影响

Study on effect of florfenicol on cytochrome P450 2E1 activity in Carassius auratus using pharmacokinetic method

以氯唑沙宗为底物探针的药物动力学方法研究氟苯尼考对鲫鱼细胞色素P450 2E1(CYP2E1)活性的影响,为临床合理用药提供参考。试验组鲫鱼每日口服氟苯尼考100 mg·kg^(-1),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^(-1),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,并计算药物动力学参数。结果表明:氯唑沙宗在2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,氟苯尼考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。

The effect of florfenicol(FFC)on the activity of cytochrome P450 2E1(CYP2E1)in Carassius auratus was e- valuated by pharmacokinetics using chlorzoxazone(CZX)as a specific substrate.FFC was administered orally for 5 days at 100 mg·(kg·d)^(-1)for the experimental group.Control fish received an equal volume of normal saline only.On day 6, fish were given an intraperitoneal injection with 10 mg·kg^(-1)CZX.The plasma concentrations of CZX were determined by HPLC.The pharmacokinetic parameters were calculated.The...