摘要
用以氯唑沙宗为底物探针的药动学方法研究了氟苯尼考和乙醇对鲫细胞色素P450 2E1活性的影响,为临床合理用药提供参考及鱼类CYP2E1的相关研究提供技术方法和理论数据。将鲫随机分为3组,即对照组、氟苯尼考组和乙醇组。实验组鲫分别每日经口给予氟苯尼考100 mg/kg.bw和乙醇1 g/kg.bw,连续5 d后,与对照组鲫同时一次性腹腔注射氯唑沙宗10 mg/kg.bw,用高效液相色谱法测定氯唑沙宗在鲫体内不同时间点的血药浓度,并计算药动学参数。结果表明氯唑沙宗在三组鲫体内的药时数据均符合二室模型;与对照组相比,氟苯尼考组和乙醇组氯唑沙宗的半衰期分别增加了5倍和0.9倍(P<0.01),药时曲线下面积分别增加了3.3倍和0.8倍(P<0.01),总清除率分别减少了83.8%和51.2%(P<0.01)。提示氟苯尼考和乙醇对鲫CYP2E1的活性具有显著的抑制作用。其它药物与其合用时,有效性和安全性可能会受到影响。
The effects of florfenicol（FFC） and ethanol（EtOH） on the activity of cytochrome P450 2E1 in Carassius auratus was investigated by pharmacokinetics using chlorzoxazone （CZX） as a specific substrate. Fish were divided into three groups as follows： FFC-treated group, EtOH-treated group and the control group. The experimental group fish received either FFC（ 100 mg/kg/day, orally） or EtOH （1 g/kg/day, orally） for 5 consecutive days. Control fish received an equal volume of normal saline only. On day 6, all groups were given an intraperitoneal injection with 10 mg/kg CZX. The plasma concentrations of CZX were determined by HPLC. The pharmacokinetic parameters were calculated. The results showed that the concentration-time data of CZX in three groups were all fitted two compartment model. Compared with the saline-treated control group, elimination half-lives were increased by 5 and 0.9 fold（P 〈0.01 ）, area under the curve were increased by 3.3 and 0.8 fold（P 〈0.01 ）, and total clearances were shortened by 83.8% and 51.2% （P 〈0.01 ） in the FFC-and EtOH-treated groups, respectively. The results indicated that the activity of CYP2E1 could be obviously inhibited by florfenicol and EtOH. Efficacy and safety profiles of a drug may be affected when concomitantly used with them.
出处
《上海水产大学学报》
CSCD
北大核心
2008年第1期34-39,共6页
Journal of Shanghai Fisheries University
基金
国家自然科学基金项目(30771626)
