乙酰甲喹在试验性肝功能损害家兔体内的药动学研究  

Pharmacokinetics of maquindox in rabbits with experimental hepatic injury

作　　者：陆晨薇[1] 李引乾[1] 关永娟[1] 张煜波[1] 白东英[1,2] 苗小楼[3] 熊永洁[1] 

机构地区：[1]西北农林科技大学动物医学院,陕西杨凌712100 [2]河南科技大学动物科技学院,河南洛阳471003 [3]中国农业科学院畜牧与兽药研究所,甘肃兰州730050

出　　处：《西北农林科技大学学报（自然科学版）》2008年第12期29-34,共6页Journal of Northwest A&F University(Natural Science Edition)

基　　金：国家“十一五”科技支撑计划项目(2006BAD04A05)

摘　　要：【目的】比较乙酰甲喹在健康和肝功能损害家兔体内的药动学特征,为临床合理用药提供资料和理论依据。【方法】将12只家兔随机均分为2组,一组为健康对照组,另一组于试验前以0.4 mL/kg剂量皮下分点注射四氯化碳,以复制肝功能损害病理模型。24 h后,对2组家兔以20 mg/kg的剂量耳缘静脉快速注射乙酰甲喹20mg/kg,6 h内不同时间心脏采血8次,用高压液相色谱法测定乙酰甲喹血药浓度,用残数法逐只家兔拟合药-时曲线,以方差分析优选房室模型计算药动学参数。【结果】乙酰甲喹在家兔体内的药动学配置符合无吸收因素一室开放模型,其药-时曲线最佳方程为:C健康=25.564 2 e-0.371 6t,C肝损=24.308 9 e-0.144t。与健康组家兔相比,肝功能损害组家兔药动学参数有显著变化:半衰期t1/2延长166.49%,消除速率常数kel减小61.25%,体清除率CLB减小54.95%,药-时曲线下面积增大155.87%。【结论】家兔肝功能损害后,乙酰甲喹在其体内的消除过程显著减慢,因此在肝脏损害时应相应减小乙酰甲喹的给药剂量或增大给药间隔时间。[Objective] The study compared the pharmacokinetics of Maquindox in control （healthy rabbits） and treated （rabbits with hepatic injury） groups to provide materials and references for clinical therapy. [Method] 12 rabbits were randomly and averagely divided into 2 groups. One was the control group,and the other one was treated with a hypodermic injection of CC14 （0.4 mL/kg） 24 h before the ex- periment for the replication of hepatic injury model. 24 h later,rabbits were treated with a rapid single-dos- age intravenous injection of Maquindox （20 mg/kg）. The blood samples were collected from heart 8 times within 6 hours after injection. The concentrations of Maquindox in serum were detected by HPLC. [Result] The results showed that the disposition of Maquindox in rabbits matched with non-absorption one-compartment open model. And the optimal concentration-time equations of the 2 groups were= C l group = 25. 564 2 e^0.3716t, Chepatic injury = 24. 308 9 e^-0.144 t. Compared with control group, t1/2 hopaticii,jory prolonged by 166.49% ;kri hepatic injury decreased by 61.25%;CLB hepatic injury decreased by 54.95%lAUC hepatic injury increased by 155.87%. [Conclusion] It can be concluded that Maquindox distributed in vivo abroad, and eliminated rapidly. The pharmacokinetics parameters of Maquindox in rabbit pathological model changed apparently,so it is necessary to lengthen the dosing interval or lessen the dosage of Maquindox on the pathological occasions.

关 键 词：乙酰甲喹 家兔 肝功能损害 药物动力学 

分 类 号：S859.53[农业科学—临床兽医学]