关键词: 华法林, 胺碘酮, 药物相互作用, VKORC1, CYP2C9

Abstract:

Warfarin has been used as anticoagulant for the long-term treatment of thromboembolic disease, however, the wide spread use is limited by a wide inter-individual variation in dose requirement. Recent studies have demonstrated that amiodarone may interact with warfarin to potentiate the anticoagulant effects and lead to an elevated international normalized ratio (INR). In addition, genetic variation in the vitamin K epoxide reductase complex subunit 1 (VKORC1) and cytochrome P450 2C9 (CYP2C9) may also affect the dose of warfarin in single or combination therapy. In our study, we aim to examine the effect of amiodarone on the warfarin in different CYP2C9 and VKORC1 status. From September 2008 to November 2009, 207 patients from Beijing, China were enrolled in our study, including 34 patients on combination therapy of amiodarone and warfarin and 173 patients on warfarin therapy. VKORCl and CYP2C9 genotypes were examined using ligation detection reaction (LDR) method. We compared the stable dosage of warfarin and INR between patients on warfarin therapy and patients on warfarin-amiodaronetherapy when they are stratified with VKORC1 or CYP2C9 genotype. We did not observe significant difference in dosage or INR between these two groups. The difference in characteristics between these two groups, the blood collection time after amiodarone administration and the method for monitoring may all contribute to the negative finding. Large studies taking into account of these factors are needed to improve our understanding of the interaction between warfarin and amiodarone, as well as the effect of genotype in such interaction.

Key words: Warfarin, Amiodarone, Drug interactions, VKORC1, CYP2C9