Creighton University School of Pharmacy and Health Professions, Omaha, Nebraska 68178, USA.
Clin Ther. 2010 Jan;32(1):53-6. doi: 10.1016/j.clinthera.2010.01.004.
Bosentan is an endothelin-receptor antagonist that reportedly induces both cytochrome P450 (CYP) 3A4 and CYP2C9 enzymes, which are also involved in warfarin metabolism. We present a case report describing a probable drug interaction between warfarin and bosentan in a patient with pulmonary hypertension.
A 52-year-old black female (weight, 77 kg) diagnosed with pulmonary hypertension secondary to bilateral pulmonary emboli had a stable international normalized ratio (INR; target range, 2-3) with a weekly warfarin dose of 52.5 mg for 2 months before the initiation of bosentan therapy. Other concurrent medications included telmisartan/ hydrochlorothiazide 40/12.5 mg once daily and a daily multivitamin (which contained no vitamin K). Three weeks after starting bosentan 62.5 mg BID, a therapeutic INR concentration was reached with a weekly warfarin dose 14% higher (an increase of 7.5 mg/wk) than her weekly warfarin dose before initiation of bosentan. After a brief discontinuation (7 days) and retitration of bosentan and warfarin, the final weekly warfarin dose (75 mg/wk) was 43% greater (an increase of 22.5 mg/wk) than the previously stable dose, which enabled the patient to reach her therapeutic INR goal range of 2 to 3.
Bosentan has CYP3A4- and CYP2C9-inducing properties and is therefore likely to cause decreased concentrations of warfarin. We describe here a probable drug interaction between bosentan and warfarin that resulted in a 43% increase in warfarin dose to maintain the patient's therapeutic INR.
波生坦是一种内皮素受体拮抗剂，据报道可诱导细胞色素 P450（CYP）3A4 和 CYP2C9 酶，这两种酶也参与华法林的代谢。我们报告了一例肺动脉高压患者华法林和波生坦之间可能发生药物相互作用的病例。
一名 52 岁黑人女性（体重 77 公斤）因双侧肺栓塞继发肺动脉高压，在开始波生坦治疗前 2 个月，华法林每周剂量为 52.5 毫克，INR（目标范围 2-3）稳定。其他同时使用的药物包括替米沙坦/氢氯噻嗪 40/12.5 毫克，每日一次，以及每日多种维生素（不含维生素 K）。开始服用波生坦 62.5 毫克 bid 后 3 周，华法林每周剂量增加 14%（每周增加 7.5 毫克），达到治疗性 INR 浓度，高于开始服用波生坦前的每周华法林剂量。短暂停药（7 天）和重新调整波生坦和华法林剂量后，最终每周华法林剂量（75 毫克/周）比之前稳定的剂量增加了 43%（每周增加 22.5 毫克），使患者达到了治疗性 INR 目标范围 2 至 3。
波生坦具有 CYP3A4 和 CYP2C9 诱导特性，因此可能导致华法林浓度降低。我们在此描述了波生坦和华法林之间可能发生的药物相互作用，导致华法林剂量增加 43%，以维持患者的治疗性 INR。
