氟尿嘧啶类抗肿瘤药物与华法林相互作用研究现状

以氟尿嘧啶类药物如5-氟尿嘧啶、卡培他滨和替吉奥等为基础的化疗方案广泛应用于各种实体瘤治疗。肿瘤患者是血栓形成的高危人群，对已发生血栓或合并血栓形成高危因素者推荐抗凝治疗。华法林是目前广泛应用的口服抗凝药。5-氟尿嘧啶、卡培他滨和替吉奥与华法林联用存在相互作用，可能导致国际标准化比值升高和出血症状，华法林停用、减量或换用低分子肝素后多数患者可恢复，少数可能需要输血治疗。氟尿嘧啶类药物与华法林相互作用的机制尚不明确，可能与5-氟尿嘧啶或其代谢产物抑制华法林代谢酶---肝细胞色素P4501C9酶活性有关。

Present status of research on drug interactions between fluoropyrimidines and warfarin

Chemotherapeutic regimens based on fluoropyrimidines such as 5-fluorouracil, capecitabine,and tegafur,gimeracil and oteracil potassium（S1）are widely used in a variety of solid tumor therapy. Cancer patients are high-risk persons of thrombosis and anticoagulant therapy is recommended for patients with thrombosis or with risk factors of thrombosis. At present,warfarin is the widely used oral anticoagulant. There are drug interactions when 5-fluorouracil, capecitabine, and S1 are given in combination with warfarin and it may lead to elevated international normalized ratio and symptoms of bleeding. Most patients could recover after warfarin withdrawal,dosage reducing,and replacement with low-molecular heparin. However, a few patients may require blood transfusion. The mechanism of drug interactions due to concomitant use of fluoropyrimidines and warfarin remains unclear and may be related to inhibiting activity of metabolic enzyme of warfarin-hepatic cytochrome P450 1C9 by 5-fluorouracil or its metabolites.