Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
Department of Internal Medicine, Admiraal de Ruyter Hospital, Goes, The Netherlands.
Clin Pharmacol Ther. 2019 Jun;105(6):1456-1461. doi: 10.1002/cpt.1331. Epub 2019 Feb 10.
Regorafenib exposure could potentially be influenced by an interaction with acid-reducing drugs. In this crossover trial, patients were randomized into two sequence groups consisting of three phases: regorafenib intake alone, regorafenib with concomitant esomeprazole, and regorafenib with esomeprazole 3 hours prior. The primary end point was the relative difference (RD) in geometric means for regorafenib 0-24-hour area under the concentration-time curve (AUC ) and was analyzed by a linear mixed model in 14 patients. AUC for regorafenib alone was 55.9 μg·hour/mL (coefficient of variance (CV): 40%), and for regorafenib with concomitant esomeprazole or with esomeprazole 3 hours prior AUC was 53.7 μg·hour/mL (CV: 34%) and 53.6 μg·hour/mL (CV: 43%), respectively. No significant differences were identified when regorafenib alone was compared with regorafenib with concomitant esomeprazole (RD: -3.9%; 95% confidence interval (CI): -20.5 to 16.1%; P = 1.0) or regorafenib with esomeprazole 3 hours prior (RD: -4.1%; 95% CI: -22.8 to 19.2%; P = 1.0). These findings indicate that regorafenib and esomeprazole can be safely combined in clinical practice.
雷戈非尼的暴露情况可能会受到与抑酸药物相互作用的影响。在这项交叉试验中，患者随机分为两组，每组有三个阶段：单独服用雷戈非尼、雷戈非尼同时服用埃索美拉唑和雷戈非尼提前 3 小时服用埃索美拉唑。主要终点是雷戈非尼 0-24 小时浓度-时间曲线下面积（AUC）的几何均值的相对差异（RD），并在 14 名患者中通过线性混合模型进行分析。单独服用雷戈非尼的 AUC 为 55.9μg·hour/mL（变异系数（CV）：40%），同时服用埃索美拉唑或提前 3 小时服用埃索美拉唑的 AUC 分别为 53.7μg·hour/mL（CV：34%）和 53.6μg·hour/mL（CV：43%）。当单独服用雷戈非尼与同时服用埃索美拉唑（RD：-3.9%；95%置信区间（CI）：-20.5 至 16.1%；P=1.0）或提前 3 小时服用埃索美拉唑（RD：-4.1%；95%CI：-22.8 至 19.2%；P=1.0）相比时，没有发现显著差异。这些发现表明，雷戈非尼和埃索美拉唑可以在临床实践中安全联合使用。
