氨氯地平与厄贝沙坦在比格犬体内的药动学相互作用

Pharmacokinetic interaction between amlodipine and irbesartan in beagle dogs

目的：探讨氨氯地平与厄贝沙坦联用时有无显著的药动学相互作用。方法：采用自身对照、随机交叉试验方法，将比格犬分为3组，每组2条，分别按试验周期服用苯磺酸氨氯地平对照药物（给药剂量以氨氯地平计5mg）、厄贝沙坦对照药物（给药剂量为250mg）和厄贝沙坦氨氯地平复方试验药物（给药剂量为以氨氯地平计5mg，厄贝沙坦250mg）。采用HPLC—ESI—MS／MS和HPLC-荧光法分别测定不同时间点氨氯地平和厄贝沙坦的血药浓度，计算药动学参数。结果：单用氨氯地平cmax为（267．63±38．49）ng／ml，AUC0-∞为（5648．71±871．68）ng·h／ml，联用氨氯地平cmax为（267．43±37．97）ng／ml，AUC0-∞。为（5751．60±924．49）ng·h／ml；单用厄贝沙坦cmax为（2623．56±198．65）ng／ml，AUC0-∞。为（10327．5．3±1522．58）ng·h／ml，联用厄贝沙坦cmax为（2345．61±42．32）ng／ml，AUG0-∞。为（10217．12±1239．13）ng·h／ml。故与两种药物分别使用的情况相比，联用时的cmax、AUC并不存在显著性差异。结论：氨氯地平与厄贝沙坦联用不存在显著的药动学相互作用。

Objective： To investigate whether there is pharmacokinetic interaction between amlodipine and irbesarta when they are administered together into beagle dogs. Methods： Six healthy adult beagle dogs were evenly divided into 3 groups according to a self-controlled randomized 2-way crossover design. Animals in 3 groups were given a single oral dose of 5 mg amlodipine powder, 250 mg irbesartan powder and compound powder of amlodipine and irbesartan （containing 5 mg amlodipine and 250 mg irbesartan）, respectively. The concentrations of amlodipine and irbesartan in beagle dog plasma were determined at specified time points by HPLC-ESI-MS/MS and HPLC-Fluorescence method, respectively; the pharmacokinetic parameters were calculated subsequently. Results： Cm,xand AUC0-∞ of amlodipine were （267.63±38.49） ng/ml and （5 648.71±871.68） ng · h/ml when administered alone and were （267.43±37.97） ng/ml and （5 751.60±924.49） ng · h/ml when combined with irbesartan,respectively. Cmaxand AUC0-∞ of irbesartan were （2 623.56±198.65） ng/ml and （10 327.53±1 522.58） ng · h/ml when administered alone and were （2 345.61±42.32） ng/ml and （10 217.12±1 239.13） ng · h/ml when combined with amlodipine,respectively. There was no significant difference in cmax and AUC of the 2 drugs when they were used alone or jointly. Conclusion： There is no obvious pharmacokinetic interaction between amlodipine and irbesarta when they are administered jointly into beagle dogs.