Department of Cardiovascular Medicine, Kitasato University School of Medicine, 1-15-1, Kitasato, Minami, Sagamihara, Kanagawa, 252-0373, Japan.
Department of Pharmacology, St. Marianna University School of Medicine, Kanagawa, Japan.
Clin Pharmacokinet. 2021 Aug;60(8):1061-1071. doi: 10.1007/s40262-021-00999-y. Epub 2021 Mar 30.
The objective of this study was to assess the pharmacokinetic and pharmacodynamic profiles and safety of edoxaban in patients with nonvalvular atrial fibrillation (NVAF) who were hospitalized with acute heart failure (AHF).
The trough plasma concentrations of edoxaban, and the coagulation biomarkers prothrombin fragments 1 and 2 (F1+2) and D-dimer, were determined. Twenty-six patients received edoxaban 60 mg (30 mg when dose adjustment was required) and blood samples were collected immediately before oral edoxaban administration for 7 consecutive days after hospitalization and on the day of discharge.
The mean observation period was 13 (range 7-46) days. Trough plasma concentrations of edoxaban were constant from day 2 onwards. On day 1, the variation was greater owing to the differing intervals between the last edoxaban dose and day 1 blood collection. Trough plasma concentrations were higher in patients with reduced creatinine clearance (≤ 50 mL/min). Median values for F1+2 and D-dimer remained within normal ranges throughout the study. There were no drug discontinuations, and no serious adverse events were reported.
This is the first study of edoxaban pharmacokinetics and pharmacodynamics in patients with NVAF and AHF, and shows that the pharmacokinetic and pharmacodynamic profiles of edoxaban were constant during hospitalization. Thus, even in patients with NVAF and AHF, edoxaban anticoagulation therapy with guided dose adjustment is considered to be a safe and appropriate intervention. In particular, patients with reduced creatinine clearance should adhere to dose adjustment criteria.
jRCTs031190006 (Japan Registry of Clinical Trials), 5 April, 2019 retrospectively registered.
本研究旨在评估非瓣膜性心房颤动（NVAF）合并急性心力衰竭（AHF）住院患者的达比加群的药代动力学和药效学特征及安全性。
测定达比加群的谷血浆浓度以及凝血生物标志物凝血酶原片段 1 和 2（F1+2）和 D-二聚体。26 例患者接受达比加群 60mg（需要剂量调整时给予 30mg），并在住院后连续 7 天及出院当天在口服达比加群前即刻采集血样。
平均观察期为 13 天（范围 7-46 天）。从第 2 天开始，达比加群的谷血浆浓度保持稳定。第 1 天，由于最后一次达比加群剂量与第 1 天采血之间的间隔不同，变化更大。在肌酐清除率降低（≤50mL/min）的患者中，达比加群的谷血浆浓度较高。整个研究过程中，F1+2 和 D-二聚体的中位数均在正常范围内。无药物停药，无严重不良事件报告。
这是第一项关于 NVAF 和 AHF 患者达比加群药代动力学和药效学的研究，表明达比加群的药代动力学和药效学特征在住院期间保持稳定。因此，即使在 NVAF 和 AHF 患者中，也可考虑在进行剂量调整指导的情况下应用达比加群进行抗凝治疗，这是一种安全且合适的干预措施。特别是肌酐清除率降低的患者，应坚持剂量调整标准。
jRCTs031190006（日本临床试验注册），2019 年 4 月 5 日回顾性注册。
