A study of pharmacokinetic interaction between diltiazem and propafenone in rabbits

Key words: 
• diltiazem /
• propafenone pharmacokinetic interaction /

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 AUC_0-∞ 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.