Chan Noel, Wheeler Matt, Bhagirath Vinai, Bosch Jacqueline, Heinrich-Nols Jutta, Sloane Debbie, van Ryn Joanne, Jefferies Linda, Wilkinson Jacqueline, Yi Qilong, Eikelboom John
Population Health Research Institute, Hamilton, Ontario, Canada.
Thrombosis and Atherosclerosis Research Institute, Hamilton, Ontario, Canada.
CJC Open. 2022 Oct 12;5(1):1-7. doi: 10.1016/j.cjco.2022.09.006. eCollection 2023 Jan.
Dabigatran is effective and safe for stroke prevention in patients with atrial fibrillation and for venous thromboembolism prevention and treatment. In Canada, APO-dabigatran, a generic formulation, has been approved based on a bioequivalence study, but its bioavailability in settings of reduced gastric acidity has not been examined.
Treatment With PO-abigatran bsorption (TADA) was an open-label crossover study in 46 healthy male volunteers, comparing the absorption of APO-dabigatran (150 mg) with vs without rabeprazole. The primary outcome was the 24-hour total dabigatran exposure as measured by area under the curve (AUC) and peak concentration (C).
Compared with no rabeprazole pretreatment, the total dabigatran AUC (geometric mean [gmean] AUC: 567.2 vs 804 ngh/mL, and gmean AUC: 609.7 vs 804) and C (gmean: 64.1 vs 104.4 ng/mL) were significantly reduced with rabeprazole. The percent gmean ratios for AUC, AUC, and C (with rabeprazole vs without) were 70.5% (95% confidence interval [CI]: 51.9% to 95.7%), 71.8% (95% CI: 53.1% to 96.9%), and 61.4% (95% CI: 44.1% to 85.5%), respectively. With rabeprazole, the proportions of participants with > 50% reduction in AUC AUC and C were 32.6%, 30.4%, and 39.1%, respectively.
When APO-dabigatran is administered with rabeprazole, the exposure to dabigatran is reduced by about 30%, which is similar to the level observed with Pradaxa when it was co-administered with a proton pump inhibitor. However, the finding that one-third of participants had a > 50% reduction in exposure is concerning, and it highlights the need for caution in patients who have, or are at risk of, reduced gastric acidity.
达比加群酯在预防心房颤动患者中风以及预防和治疗静脉血栓栓塞方面有效且安全。在加拿大，一种通用制剂APO-达比加群酯已基于生物等效性研究获得批准，但其在胃酸降低情况下的生物利用度尚未得到检验。
口服达比加群酯吸收治疗（TADA）是一项针对46名健康男性志愿者的开放标签交叉研究，比较了服用雷贝拉唑与未服用雷贝拉唑时APO-达比加群酯（150毫克）的吸收情况。主要结局是通过曲线下面积（AUC）和峰浓度（C）测量的24小时达比加群酯总暴露量。
与未进行雷贝拉唑预处理相比，服用雷贝拉唑时达比加群酯的总AUC（几何均值[gmean] AUC：567.2对804纳克/毫升，以及gmean AUC：609.7对804）和C（gmean：64.1对104.4纳克/毫升）显著降低。AUC、AUC和C的gmean百分比比值（服用雷贝拉唑与未服用相比）分别为70.5%（95%置信区间[CI]：51.9%至95.7%）、71.8%（95%CI：53.1%至96.9%）和61.4%（95%CI：44.1%至85.5%）。服用雷贝拉唑时，AUC、AUC和C降低超过50%的参与者比例分别为32.6%、30.4%和39.1%。
当APO-达比加群酯与雷贝拉唑联用时，达比加群酯的暴露量降低约30%，这与Pradaxa与质子泵抑制剂联用时观察到的水平相似。然而，三分之一的参与者暴露量降低超过50%这一发现令人担忧，它凸显了对有胃酸降低情况或有胃酸降低风险的患者需谨慎用药。
