地尔硫■与普罗帕酮在家兔体内的药动学相互作用研究  

A study of pharmacokinetic interaction between diltiazem and propafenone in rabbits

作　　者：印绮平[1] 王宏图[1] 张静华[1] 施孝金[1] 

机构地区：[1]上海医科大学华山医院临床药学研究室

出　　处：《药学实践杂志》1995年第6期355-357,共3页Journal of Pharmaceutical Practice

摘　　要：６只家兔随机交叉实验，分别单用地尔硫、普罗帕酮或合用两药，结果发现合用两药后，普罗帕酮的消除速率常数Ｋｅ和清除率ｃｌｓ／Ｆ较单用时明显减小，消除半衰期ｔ１／２（ｋｅ）平均延长０．７０１小时，第一峰浓度和第二峰浓度分别升高８５．７４％和７５．５５％，ＡＶＣ０－∞增大５６．７５％，且均有显著性意义。地尔硫的ｃｌｓ／Ｆ在合用药后显著降低，Ｖｄ／Ｆ显著减小，地尔硫及其活性代谢物去乙酰地尔硫的峰浓度则分别增大１２９．８３％和１１９．１３％。表明两药合用后普罗帕酮的肝脏代谢受到抑制，同时普罗帕酮也影响了地尔硫的体内吸收或处置过程。提示临床两药合用时应同时监测患者血浓，避免不良反应的发生。A balanced, randomized and crossover study was conducted in six rabbits. Each rabbit was given diltiazem/propafenone alone or in combination. Pharmacokinetic parameters of propafenone were significantly changed when coadministration with diltiazem. Its Ke and cls/F were both Cmax and AUC0-∞ were increased. On the other hand, some pharmacokinetic parameters of diltiazem were also changed after combination treatment. Its cls/F and Vd/F were both decreased,while its Cmax was elevated. In addition, Cmax of deacetyldiltiazem,an active metabolite of diltiazem, was also elevated.It was suggested that the metabolism of propafenone in liver may be inhibited by diltiazem and meanwhile propafenone may have an effect on the absorption or elimination of diltiazem. From the above result, it is essential for clinicians to monitor drug concentration when diltiazem is coadministed with propafenone,and in some case, dosage of these drugs should be adjusted.

关 键 词：地尔硫卓 普罗帕酮 药物相互作用 药物动力学 

分 类 号：R972[医药卫生—药品]