Kong A N, Tomasko L, Waldman S A, Osborne B, Deutsch P J, Goldberg M R, Bjornsson T D
Department of Medicine, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
J Clin Pharmacol. 1995 Oct;35(10):1008-15. doi: 10.1002/j.1552-4604.1995.tb04018.x.
Losartan, on orally active, nonpeptide angiotensin II receptor antagonist is being developed as a therapeutic agent for the treatment of hypertension and heart failure. Many patients requiring anticoagulant therapy with warfarin also may have hypertension or heart failure, and thus, are potential candidates for losartan therapy. This study was designed to investigate whether losartan at likely dosage levels would alter the anticoagulant response to warfarin. In a two-period, placebo-controlled, randomized, crossover study, ten healthy male subjects received a single oral dose of 30 mg warfarin sodium on the seventh day of a 13-day treatment with losartan, 100 mg daily by mouth, or placebo. Multiple plasma samples were collected over a 6-day period after both warfarin doses for the measurements of R- and S-warfarin concentrations and prothrombin times. The pharmacokinetics of R- and S-warfarin were comparable in the absence and presence of losartan (no significant effects of losartan on area under the curve, Cmax, or tmax). Losartan also had no significant effect on the anticoagulant effect of warfarin, as assessed by the area under the prothrombin time versus time curve and the maximum response for prothrombin time. The lack of pharmacokinetic or pharmacodynamic interaction between warfarin and losartan observed in this investigation suggests that a clinically important interaction between these drugs is unlikely to occur in patients requiring concomitant administration of both drugs.
氯沙坦是一种口服活性非肽类血管紧张素 II 受体拮抗剂，正作为治疗高血压和心力衰竭的治疗药物进行研发。许多需要使用华法林进行抗凝治疗的患者也可能患有高血压或心力衰竭，因此，他们是氯沙坦治疗的潜在候选者。本研究旨在调查氯沙坦在可能的剂量水平下是否会改变对华法林的抗凝反应。在一项为期两个阶段、安慰剂对照、随机、交叉研究中，10 名健康男性受试者在接受氯沙坦（每日口服 100 mg）或安慰剂为期 13 天的治疗的第 7 天，单次口服 30 mg 华法林钠。在两次服用华法林后的 6 天内采集多个血浆样本，用于测量 R-和 S-华法林浓度以及凝血酶原时间。在不存在和存在氯沙坦的情况下，R-和 S-华法林的药代动力学具有可比性（氯沙坦对曲线下面积、Cmax 或 tmax 无显著影响）。通过凝血酶原时间与时间曲线下面积和凝血酶原时间的最大反应评估，氯沙坦对华法林的抗凝作用也无显著影响。在本研究中观察到华法林与氯沙坦之间缺乏药代动力学或药效学相互作用，这表明在需要同时使用这两种药物的患者中，这两种药物之间不太可能发生具有临床重要性的相互作用。
