Beagle犬给予单、复方苯磺酸氨氯地平/氯沙坦钾片后有效成分氨氯地平、氯沙坦及其代谢产物EXP3174的药动学研究  

The Pharmacokinetics of Amlodipine,Losartan and Its Metabolite EXP3174 in Beagle Dogs After Administrating Single or Compound Tables

作　　者：刘茜[1] 刘艳芳[1] 赵辉[1] 刘洋[1] 张旭[1] 王书典 

机构地区：[1]沈阳药科大学药物分析教研室,沈阳110000 [2]北京韩美药品有限公司,北京101312

出　　处：《中国药学杂志》2012年第14期1139-1143,共5页Chinese Pharmaceutical Journal

摘　　要：目的比较氨氯地平、氯沙坦及其代谢产物EXP3174 3种物质在单、复方制剂给予Beagle犬时的药动学差别。方法采用LC-MS/MS法,分别测定6只Beagle犬交叉口服单方或复方制剂后血浆中氨氯地平、氯沙坦及其代谢产物EXP3174的浓度,应用DAS软件计算药动学参数。结果①单方和复方制剂中氯沙坦主要药动学参数:tmax(1.36±0.46)和(1.03±0.27)h;ρmax(905±477)和(1 009±440)ng.mL-1;AUC0-t(1 556±696)和(1 601±432)ng.h.mL-1。②单方和复方制剂中EXP3174的主要药动学参数:tmax(1.67±0.41)和(1.42±0.38)h;ρmax(69.2±48.1)和(47.1±14.6)ng.mL-1;AUC0-t(191±120)和(142±80.6)ng.h.mL-1。③单方和复方制剂中氨氯地平的主要药动学参数:tmax(2.75±0.61)和(3.00±0.95)h;ρmax(38.5±14.9)和(33.8±8.05)ng.mL-1;AUC0-t(467±163)和(438±141)ng.h.mL-1。结论单、复方苯磺酸氨氯地平/氯沙坦钾片在Beagle犬体内的主要有效成分氨氯地平、氯沙坦及其代谢产物EXP3174的各药动学参数均不存在显著性差异。OBJECTIVE To compare the pharmacokinetic difference of amlodipine, losartan and its metabolite EXP3174 between single and compound tables in Beagle dogs. METHODS Amlodipine besylate tablet, losartan potassium tablet and compound amlo- dipine besylate/losartan potassium tablet were given to six Beagle dogs in a randomized crossover way, then the concentrations of amlo- dipine, losartan and its metabolite EXP3174 were determined by LC-MS/MS, and the main pharmacokinetics parameters were analyzed by DAS software. RESULTS The main pharmacokinetic parameters of losartan in single and compound tablets were as follows： tmax （ 1.36 ± 0. 46 ） and （ 1.03 ± 0. 27 ） h ; Pmax （ 905± 477 ） and （ 1 009 ± 440） ng·mL^-1 ; AUC0.t （ 1 556 ± 696 ） and （ 1 601 ± 432 ） ng ·h · mL^-1. The main pharmacokinetic parameters of EXP3174 in single and compound tablets were as follows： tmax（ 1. 67 ＋0. 41 ） and（1.42±0.38）h;pmax（69.2±48.1）and（47.1 ±14.6）ng · mL^-1; AUC0-t（191 ±120 ） and （142 ± 80. 6 ） ng ·h ·mL^-1. The main pharmacokinetic parameters of amlodipine in single and compound tablets were as follows： tmax （2. 75 ± 0. 61 ）and（3.00 ± 0. 95 ） h; pmax（38. 5 ± 14. 9）and（33.8 ±8.05）ng · mL^-1 ; AUC0-t（467 ± 163） and（438 ± 141 ）ng·h· mL^-1. CONCLUSION There are no significant differences in pharmacokinetic parameters of amlodipine besylate, losartan potassium and its metabolite EXP3174 between their single and comoound tablets in beazle dogs.

关 键 词：氨氯地平 氯沙坦 EXP3174 液相色谱-串联质谱法 药动学 

分 类 号：R972.4[医药卫生—药品]