氨氯地平与厄贝沙坦在比格犬体内的药动学相互作用
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上海市药物(中药)代谢产物研究重点实验室资助课题(036505016).


Pharmacokinetic interaction between amlodipine and irbesartan in beagle dogs
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Supported by the Program of Shanghai Key Laboratory for Pharmaceutical Metabolites Research(Traditional Chinese Medicine) (036505016).

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    摘要:

    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5 mg)、厄贝沙坦对照药物(给药剂量为250 mg)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5 mg,厄贝沙坦250 mg).采用HPLCESI-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(5 648.71±871.68)ng·h/ml,联用氨氯地平cmax为(267.43±37.97)ng/ml,AUC0~∞为(5 751.60±924.49)ng·h/ml;单用厄贝沙坦cmax为(2 623.56±198.65)ng/ml,AUC0~∞为(10 327.53±1 522.58)ng·h/ml,联用厄贝沙坦cmax为(2 345.61±42.32)ng/ml,AUC0~∞为(10 217.12±1 239.13)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.

    Abstract:

    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.

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  • 收稿日期:2006-04-10
  • 最后修改日期:2006-05-30
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  • 在线发布日期: 2006-07-20
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