Wilson Jo-Anne S, Goralski Kerry B, Soroka Steven D, Morrison Matthew, Mossop Paula, Sleno Lekha, Wang Yan, Anderson David R
College of Pharmacy, Faculty of Health Professions, Dalhousie University, Halifax, Nova Scotia, Canada; Division of Nephrology, Department of Medicine, Capital District Health Authority, Halifax, Nova Scotia, Canada.
J Clin Pharmacol. 2014 Aug;54(8):901-9. doi: 10.1002/jcph.335. Epub 2014 May 28.
Dabigatran etexilate represents a possible improved alternative to warfarin for anticoagulation in hemodialysis patients with atrial fibrillation (AF). The objective was to determine dabigatran plasma concentrations and anticoagulant effects following administration of a single 110 mg oral dose of dabigatran etexilate to 10 adult patients immediately prior to starting hemodialysis. Mass spectrometry and the Hemoclot® assay were used, respectively, to determine free (unconjugated) dabigatran concentrations and thrombin time (TT) in plasma samples collected intermittently over 48 hours. The median time (tmax ) to reach the maximum plasma-free dabigatran concentration (Cmax ) was 2 hours (range 1-3 hours). The mean free dabigatran Cmax was 95.5 ± 33.4 ng/mL. The mean elimination half-lives on and off hemodialysis were, respectively, 2.6 ± 1.3 and 30.2 ± 7.8 hours. Hemodialysis effectively removed dabigatran with an extraction ratio of 0.63 ± 0.07. The maximal TT ratio was 2.1 and the TT ratio demonstrated a strong linear dependence on free dabigatran concentration (r(2) = 0.741). A 110 mg oral dabigatran dose prior to hemodialysis was rapidly absorbed and achieved therapeutic concentrations. Hemodialysis effectively removed dabigatran from the plasma and may be an effective means of accelerating the elimination of dabigatran in circumstances of excessive anticoagulation.
达比加群酯可能是华法林在心房颤动（AF）血液透析患者抗凝治疗方面的一种改良替代药物。目的是确定在10名成年患者开始血液透析前立即口服单次110mg达比加群酯后达比加群的血浆浓度和抗凝效果。分别使用质谱法和Hemoclot®检测法，测定在48小时内间歇性采集的血浆样本中游离（未结合）达比加群浓度和凝血酶时间（TT）。达到最大血浆游离达比加群浓度（Cmax）的中位时间（tmax）为2小时（范围1 - 3小时）。游离达比加群的平均Cmax为95.5±33.4 ng/mL。血液透析期间和非透析期间的平均消除半衰期分别为2.6±1.3小时和30.2±7.8小时。血液透析有效清除达比加群，清除率为0.63±0.07。最大TT比值为2.1，且TT比值与游离达比加群浓度呈强线性相关（r(2)=0.741）。血液透析前口服110mg达比加群剂量吸收迅速并达到治疗浓度。血液透析可有效从血浆中清除达比加群，在抗凝过度的情况下可能是加速达比加群清除的有效手段。
