【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。更多还原

【Abstract】 OBJECTIVE To investigate the pharmacokinetic parameters of clenbuterol at toxic dosage, to assess its difference of pharmacokinetic 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 pharmacokinet parameters. RESULTS The concentration-time profiles of clenbuterol of both dosages were best fitted to one –compartment open model.The main pharmacokinetic parameters of toxic (150μg·kg^-1) and theraputic (5μg·kg^-1) dosages were as follows: Ke was 0.39±0.08, 0.18±0.07 h^-1, respectively;t_1/2（ke） was 1.82±0.34, 4.30±1.61h, respectively;t_1/2（ka） was 0.67±0.28,1.05±（0.28） h, respectively;t_max was （1.48±0.39）,（2.70±0.22）h, respectively;C_max 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）,t_1/2（ka） （P<0.05）,t_1/2（ke） （P<0.05）,t_max （P<0.01）,MRT（P<（0.01）） showed significant difference between two dosages. C_maxand AUC were increased with the dosages. C_max/D₀ and AUC/D₀ didn’t show significant difference between two dosages（P>0.05）.更多还原