新型口服抗凝药的药物相互作用

Drug interactions of new oral anticoagulants

新型口服抗凝药(NOACs,达比加群酯、利伐沙班、阿哌沙班、依度沙班)与华法林相比,起效更快且剂量固定,具有更宽的治疗窗口和更少的药物或食物相互作用及同等或更高的安全性等优点,现被广泛应用于临床。考虑它们是P-糖化蛋白和(或)代谢酶P450的底物,又具有抗凝功效,针对NOACs的药物相互作用的探索是近几年来国际上的研究热点。从药动学角度出发,NOACs与许多药物存在药物相互作用。其中,NOACs与P-gp和CYP3A4的强效抑制剂存在显著的药物相互作用,且具有临床相关性;与质子泵抑制剂和心血管药物存在主要的药物相互作用。从药效学角度出发,NOACs与非甾体抗炎药、抗凝药物、抗血小板聚集药物也有潜在药物相互作用。本文主要从药动学和药效学两方面综述了NOACs与临床常用药物和天然药物之间的相互作用,旨在为临床医师合理用药提供参考。

New oral anticoagulants(NOACs, dabigatran etexilate, rivaroxaban, apixaban & edoxaban) are widely applied in clinical practices due to their faster onset and fixed dose, wider treatment window, less drug or food interaction and equal or higher safety as compared with warfarin. Considering that they are substrates of P-glycoprotein and/or metabolizing enzyme P450 with anticoagulant properties, research on drug-drug interactions(DDIs) of NOACs has become a hotspot in recent years. From a pharmacokinetic point of view, NOACs have drug interactions with many drugs. Among them, NOACs have significant drug interactions with potent inhibitors of P-gp and CYP3 A4 and there was clinical correlation. There are major drug interactions with proton pump inhibitors and cardiovascular agents. From the perspective of pharmacodynamics, NOACs also have potential drug interactions with non-steroidal anti-inflammatory drugs, anticoagulants and anti-platelet aggregation drugs. This paper reviewed the PK & PD interactions of NOACs with common clinical and natural drugs and it provided a handy reference for clinical physicians in rational drug dosing.