Hoerr Robert, Zimmermann Andrea, Seitz Friedeborg, Dienel Angelika
Dr. Willmar Schwabe GmbH & Co. KG, Research and Development, Karlsruhe, Germany.
Dr. Willmar Schwabe GmbH & Co. KG, Biometry Department, Karlsruhe, Germany.
Front Pharmacol. 2022 Apr 20;13:868843. doi: 10.3389/fphar.2022.868843. eCollection 2022.
The present drug-drug interaction study investigates whether single or repeated doses of 240 mg extract EGb 761 alter the pharmacokinetics or pharmacodynamics of rivaroxaban in healthy subjects. This was a single-centre, two-period, fixed-sequence trial. In Period 1, rivaroxaban was taken alone. In Period 2, rivaroxaban was given on the first and last of 8 days of EGb 761 treatment. Plasma concentrations of rivaroxaban and anti-Factor Xa activity were determined until 48 h after each rivaroxaban intake. The data of forty-one healthy subjects (25 males, 16 females) aged 21-70 years were evaluable. Geometric mean ratios (90% confidence intervals) for rivaroxaban administered concomitantly with a single or multiple doses of EGb 761 vs. rivaroxaban administered alone were 97.97 (91.78, 104.58) and 96.78 (90.67, 103.31) for maximum concentration (C), 98.55 (94.43, 102.84) and 97.82 (93.73, 102.08) for area under the concentration-time curve (AUC) of rivaroxaban in plasma (primary endpoints), 98.19 (92.00, 104.80) and 99.78 (93.43, 106.55) for maximum effect (E), 99.46 (93.63, 105.66) and 99.12 (93.25, 105.35) for area under the effect curve (AUEC). All 90% confidence intervals were within the prespecified range of 80%-125%. Neither adverse events related to haemorrhages nor clinically significant findings in haematology or coagulation parameters were observed. The treatments were safe and well-tolerated. Single and repeated doses of EGb 761® neither affect plasma concentrations of rivaroxaban nor anti-Factor Xa activity in healthy subjects.
本药物相互作用研究旨在调查单剂量或重复剂量的240毫克银杏叶提取物EGb 761是否会改变健康受试者中利伐沙班的药代动力学或药效学。这是一项单中心、两阶段、固定顺序试验。在第1阶段，单独服用利伐沙班。在第2阶段，在EGb 761治疗的8天中的第1天和最后一天给予利伐沙班。在每次服用利伐沙班后48小时内测定利伐沙班的血浆浓度和抗Xa因子活性。41名年龄在21至70岁之间的健康受试者（25名男性，16名女性）的数据可用于评估。与单剂量或多剂量EGb 761联合给药的利伐沙班与单独给药的利伐沙班相比，最大浓度（C）的几何平均比值（90%置信区间）分别为97.97（91.78，104.58）和96.78（90.67，103.31），血浆中利伐沙班浓度-时间曲线下面积（AUC）的几何平均比值分别为98.55（94.43，102.84）和97.82（93.73，102.08）（主要终点），最大效应（E）的几何平均比值分别为98.19（92.00，104.80）和99.78（93.43，106.55），效应曲线下面积（AUEC）的几何平均比值分别为99.46（93.63，105.66）和99.12（93.25，105.35）。所有90%置信区间均在预先指定的80%-125%范围内。未观察到与出血相关的不良事件，也未观察到血液学或凝血参数方面具有临床意义的结果。这些治疗是安全且耐受性良好的。单剂量和重复剂量的EGb 761均不会影响健康受试者中利伐沙班的血浆浓度或抗Xa因子活性。
