Details

Autor(en) / Beteiligte

• Man, Femke M.
• Hussaarts, Koen G.A.M.
• With, Mirjam
• Oomen‐de Hoop, Esther
• Bruijn, Peter
• Halteren, Henk K.
• Burg‐de Graauw, Nicole C.H.P.
• Eskens, Ferry A.L.M.
• Gelder, Teun
• Leeuwen, Roelof W.F.
• Mathijssen, Ron H.J.

Titel

Influence of the Proton Pump Inhibitor Esomeprazole on the Bioavailability of Regorafenib: A Randomized Crossover Pharmacokinetic Study

Ist Teil von

• Clinical pharmacology and therapeutics, 2019-06, Vol.105 (6), p.1456-1461

Ort / Verlag

United States: John Wiley and Sons Inc

Erscheinungsjahr

2019

Quelle

Wiley Online Library Journals Frontfile Complete

Beschreibungen/Notizen

• 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 (AUC0–24h) and was analyzed by a linear mixed model in 14 patients. AUC0–24h 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 AUC0–24h 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.