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%,且均有显着性意义。地尔硫的cls/F在合用药后显着降低,Vd/F显着减小,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。
Abstract:
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.