Nakano Takafumi, Nakamura Tomomi, Nakamura Yoshihio, Irie Keiichi, Sato Keisuke, Matsuo Kohichi, Imakyure Osamu, Ogata Kentaro, Mishima Kenichi, Kamimura Hidetoshi
Department of Pharmacy, Fukuoka University Hospital.
Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University.
Yakugaku Zasshi. 2017;137(7):909-916. doi: 10.1248/yakushi.17-00023.
Warfarin (WF) shows a number of interactions with other drugs, which alter its anticoagulant effects. The albumin binding interaction is one such pharmacokinetic mechanism of drug interaction with WF, which induces a rise in the free WF concentration and thus increases the risk of WF toxicity. Teicoplanin (TEIC) is an anti-methicillin-resistant Staphylococcus aureus drug, which also binds strongly to albumin in the plasma. Therefore, co-administration of TEIC may displace WF from the albumin binding site, and possibly result in a toxicity. The present study was performed to investigate the drug-drug interaction between WF and TEIC in comparison with controls treated with vancomycin (VCM), which has the same spectrum of activity as TEIC but a lower albumin binding ratio.The records of 49 patients treated with WF and TEIC or VCM at Fukuoka University Hospital between 2010 and 2015 were retrospectively reviewed. These 49 patients consisted of 18 treated with TEIC in combination with WF, while 31 received VCM in combination with WF. Prothrombin time-international normalized ratio (PT-INR) showed a significant increase of 80.9 (52.0-155.3) % after co-administration of TEIC with WF. In contrast, the rate of PT-INR elevation associated with VCM plus WF was 30.6 (4.5-44.1) %. These observations suggested that TEIC can cause a rise in free WF concentration by albumin binding interaction. Therefore, careful monitoring of PT-INR elevation is necessary in patients receiving WF plus TEIC.
华法林（WF）与其他药物存在多种相互作用，这些相互作用会改变其抗凝效果。白蛋白结合相互作用是药物与WF相互作用的一种药代动力学机制，它会导致游离WF浓度升高，从而增加WF毒性风险。替考拉宁（TEIC）是一种抗耐甲氧西林金黄色葡萄球菌药物，它也与血浆中的白蛋白紧密结合。因此，联合使用TEIC可能会将WF从白蛋白结合位点上置换出来，并可能导致毒性反应。本研究旨在调查WF与TEIC之间的药物相互作用，并与使用万古霉素（VCM）治疗的对照组进行比较，VCM与TEIC具有相同的活性谱，但白蛋白结合率较低。对2010年至2015年期间在福冈大学医院接受WF和TEIC或VCM治疗的49例患者的记录进行了回顾性分析。这49例患者中，18例接受TEIC与WF联合治疗，31例接受VCM与WF联合治疗。TEIC与WF联合给药后，凝血酶原时间-国际标准化比值（PT-INR）显著升高80.9（52.0 - 155.3）%。相比之下，VCM加WF导致PT-INR升高的比率为30.6（4.5 - 44.1）%。这些观察结果表明，TEIC可通过白蛋白结合相互作用导致游离WF浓度升高。因此，接受WF加TEIC治疗的患者有必要仔细监测PT-INR升高情况。
