Department of Pharmacy, National Taiwan University Hospital, Taipei, Taiwan; School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan.
Stroke Center and Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan.
J Formos Med Assoc. 2019 Jul;118(7):1154-1160. doi: 10.1016/j.jfma.2018.11.013. Epub 2018 Dec 21.
BACKGROUND/PURPOSE: Dabigatran is effective in preventing ischemic stroke and systemic embolism in patients with atrial fibrillation. Although the therapeutic window for dabigatran is wide, its pharmacokinetic properties can differ between specific populations. This study aimed to establish a real-life plasma dabigatran concentration database and investigate potential factors affecting this concentration in Asians.
Patients under dabigatran therapy were recruited. Plasma dabigatran concentration was determined in trough and peak blood samples by using ultra-high performance liquid chromatography with tandem mass spectrometry analysis. Factors affecting the dabigatran concentration were investigated.
A total of 46 patients (33 male, 71.7%) were prospectively enrolled. Most of them were receiving a low dose regimen (110 mg twice daily, n = 38, 82.6%). The trough and peak concentrations were significantly correlated (p < 0.001), and the trough concentration was higher in patients aged ≥75 years, body weight ≤60 kg, creatinine clearance (CrCl) ≤50 mL/min, CHADS-VASc score >3 points, and HAS-BLED score ≥3 points. Multiple linear regression analysis identified body weight and serum creatinine as key factors predicting trough concentration (p = 0.003 and 0.005, respectively). Importantly, drug adherence was the only independent factor associated with low trough concentration, defined as the lowest 20th percentile in our study cohort (n = 10, hazard ratio = 9.07; 95% CI, 1.12 to 73.22; p = 0.004).
Dabigatran monitoring may be considered for patients at risk of overexposure, especially those with low body weight and renal insufficiency, and also for detecting those with extremely low drug concentration.
背景/目的：达比加群酯可有效预防房颤患者发生缺血性卒中和全身性栓塞。尽管达比加群酯的治疗窗较宽，但在特定人群中其药代动力学特性可能存在差异。本研究旨在建立真实世界的达比加群血浆浓度数据库，并探讨影响亚洲人群达比加群浓度的潜在因素。
招募正在接受达比加群治疗的患者。采用超高效液相色谱-串联质谱法分析在谷值和峰值时的血浆达比加群浓度。研究影响达比加群浓度的因素。
共前瞻性纳入 46 例患者（33 例男性，71.7%）。大多数患者接受低剂量方案（110 mg，每日 2 次，n = 38，82.6%）。谷值和峰值浓度呈显著相关性（p < 0.001），年龄≥75 岁、体重≤60 kg、肌酐清除率（CrCl）≤50 mL/min、CHADS-VASc 评分>3 分和 HAS-BLED 评分≥3 分的患者谷值浓度更高。多元线性回归分析确定体重和血清肌酐是预测谷值浓度的关键因素（p = 0.003 和 0.005）。重要的是，药物依从性是与低值谷浓度相关的唯一独立因素，低值谷浓度定义为本研究队列中最低的第 20 百分位数（n = 10，风险比 = 9.07；95%CI，1.12 至 73.22；p = 0.004）。
对于有药物过量风险的患者，特别是体重较低和肾功能不全的患者，以及检测药物浓度极低的患者，可能需要进行达比加群监测。
