中毒剂量与治疗剂量克仑特罗在兔体内的药动学研究  

A study on the pharmacokinetics of clenbuterol at toxic and therapeutic dosage in rabbits

作　　者：陈一农[1] 张吟[1] 郑兴中[1] 颜文祝[1] 

机构地区：[1]福建医科大学附属第二医院,福建泉州362000

出　　处：《中国现代应用药学》2005年第4期272-275,共4页Chinese Journal of Modern Applied Pharmacy

摘　　要：目的研究克仑特罗在引起不良反应的大剂量下兔体内的药动学,探讨中毒剂量与治疗剂量的药动学参数存在的差异。方法新西兰兔单剂量灌胃(ig)中毒剂量(150μg·kg-1)与治疗剂量(5μg·kg-1)的盐酸克仑特罗溶液,采用酶标免疫分析(ELISA)测定不同时间的血浆药物浓度。两组试验数据采用3P97程序拟合处理,求得不同剂量的药动学参数。结果两组剂量的浓度-时间曲线均符合一室开放模型。中毒剂量与治疗剂量的Ke分别为(0.39±0.08)h-1和(0.18±0.07)h-1;t1/2(ke)分别为(1.82±0.34)h和(4.30±1.61)h;t1/2(ka)分别为(0.67±0.28)h和(1.05±0.28)h;t(max)分别为(1.48±0.39)h和(2.70±0.22)h;Cmax分别为(71.37±37.76)ng·mL-1和(1.56±0.98)ng·mL-1;AUC分别为(310.28±115.00)ng·h·mL-1和(14.28±7.22)ng·h·mL-1;MRT分别为(3.74±0.51)h和(8.82±2.78)h。结论两组剂量在Ke(P<0.01),t1/2(ka)(P<0.05),t1/2(ke)(P<0.05)、tmax(P<0.01),MRT(P<0.01)等存在显著差异;Cmax,AUC随剂量增加而增加,Cmax/D0、AUC/D0无显著性差异(P>0.05),为临床抢救中毒病人提供参考。OBJECTIVE To investigate the pharmacokinetic parameters of clenbuterol at toxic dosage, to assess its difference of pharmaeokinetie parameters between toxic and therapeutic dosages. METHODS The new Zealand white rabbits of two groups were given 150μg · kg^-1 and 5μg · kg^-1 bw of clenbuterol by ig administration respectively. The concentrations of clenbuterol in plasma were determined by ELISA at given times after administration. The data of two groups were processed by 3P97 program to calculate their pharmaeokinet parameters. RESULTS The concentration-time profiles of elenbuterol of both dosages were best fitted to onecompartment open model. The main pharmaeokinetie parameters of toxic （ 150μg· kg^-1 ） and theraputie （5μg· kg^-1 ） dosages were as follows ： Ke was 0.39 ± 0.08, 0.18 ±0.07 h^ -1, respectively ; t1/2（ ke） was 1. 82 ± 0.34, 4.30 ± 1.61 h, respectively ; t1/2（ke） was 0.67 ±0.28, 1.05 ± 0.28 h, respectively ; tmax was （ 1.48 ± 0.39 ） , （ 2.70± 0.22 ） h, respectively ; Cmax was 71.37 ± 37.76,1.56 ± 0.98 ng·mL^-1 , respectively; AUC was 310.28 ± 115.00, 14.28 ±7.22 ng · h · mL^-1 , respectively; MRT was 3.74 ±0.51, 8.82 ±2.78h, respectively. CONCLUSION The parameters such as Ke （P〈0.01）, t1/2〈（ke） （P〈0.05）,t1/2〈（ke） （P 〈0.05） ,tmax（P〈0.01） ,MRT（P 〈 0.01 ） showed significant difference between two dosages. Cmax and AUC were increased with the dosages. Cmax/D0 and AUC/D0 didn＇t show significant difference between two dosages（ P 〉0.05 ）.

关 键 词：克仑特罗(瘦肉精) 药动学 中毒剂量 治疗剂量 酶标免疫分忻 血浆药物浓度 

分 类 号：F971[经济管理] R969.1[医药卫生—药理学]